Experiments are often performed to study the behaviour of a single ion channel in response to a perturbation produced by a step change (jump) in a variable that influences its equilibrium position, for example a voltage jump or jump in agonist concentration. It is also common to apply a rectangular pulse (consisting of an on jump followed by an off jump); for example brief concentration pulses are used to mimic synaptic transmission.. Assuming a general Markov mechanism for channel dynamics, we obtain theoretical probability distributions of observable characteristics that describe the non-stationary behaviour of single ion channels which are subject to a jump, or to a pulse of finite duration. These characteristics are such things as open times, shut times, first latency, burst length and length of activation. We concentrate particularly on jumps to or from a zero level of agonist, which necessitates some modification to the usual arguments to cope with having some absorbing sets of states. ...
A common concern regarding the use of Xenopus oocytes for the heterologous expression of ion channels is the presence of endogenous channels, which may complicate single-channel studies by providing unwanted background signal (Sobczak et al., 2010; Terhag et al., 2010). An important consideration for our studies was potential interference by endogenous mechanosensitive channels, which have been reported in both excised and cell-attached patches of Xenopus ootyes (Methfessel et al., 1986; Taglietti and Toselli, 1988; Yang and Sachs, 1990; Lane et al., 1991). However, as shown in Fig. 1 B, although endogenous mechanosensitive channels are frequently present in cell-attached patches, they are not active in excised patches under our conditions. Although we cannot completely rule out a minor effect of endogenous channels on our recordings, their contribution to the final conductance measured under tension appears negligible; in traces at relatively high tensions, with all MscS single-channel events ...
P2X receptors are cation-selective ion channels gated by extracellular ATP, and are implicated in diverse physiological processes, from synaptic transmission to inflammation to the sensing of taste and pain. Because P2X receptors are not related to other ion channel proteins of known structure, there is at present no molecular foundation for mechanisms of ligand-gating, allosteric modulation and ion permeation. Here we present crystal structures of the zebrafish P2X4 receptor in its closed, resting state. The chalice-shaped, trimeric receptor is knit together by subunit-subunit contacts implicated in ion channel gating and receptor assembly. Extracellular domains, rich in β-strands, have large acidic patches that may attract cations, through fenestrations, to vestibules near the ion channel. In the transmembrane pore, the gate is defined by an ∼8 Å slab of protein. We define the location of three non-canonical, intersubunit ATP-binding sites, and suggest that ATP binding promotes subunit
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Voltage-gated ion channels play fundamental roles in excitable cells, such as neurons, where they enable electric signaling. Normally, this signaling is well controlled, but brain damage, alterations in the ionic composition of the extracellular solution, or dysfunctional ion channels can increase the electrical excitability thereby causing epilepsy. Voltage-gated ion channels are obvious targets for antiepileptic drugs, and, as a rule of thumb, excitability is dampened either by closing voltagegated sodium channels (Nav channels) or by opening voltage-gated potassium channels (Kv channels). For example, several classical antiepileptic drugs block the ion-conducting pore of Nav channels. Despite the large number of existing antiepileptic drugs, one third of the patients with epilepsy suffer from intractable or pharmacoresistant seizures.. Our research group has earlier described how different polyunsaturated fatty acids (PUFAs) open a Kv channel by binding close to the voltage sensor and, from ...
The cGMP-dependent channel protein has been purified from bovine rod photoreceptor membranes and incorporated into planar lipid membranes. At low divalent cation concentrations, cGMP stimulated single-channel current fluctuations. The probability Po of the channel being open strongly depended on the cGMP concentration (EC50 = 31 microM; Hill coefficient, n = 2.3); whereas the single-channel conductance (lambda = 26 pS) was independent of the agonist concentration. The agonist-stimulated increase in the probability of an open channel was largely due to shorter closed times and, to a lesser extent, due to the channel staying open for a longer time. The current-voltage relationship of the single open channel deviated from ohmic behavior, and the open probability decreased at more negative membrane potentials. The rectification of the macroscopic cGMP-induced current in artificial bilayers that contained many channel copies can be accounted for by the voltage dependence of channel gating together ...
Neuronal ion channels are gated pores whose opening and closing is usually regulated by factors such as voltage or ligands. They are often selectively permeable to ions such as sodium, potassium or calcium. Rapid signalling in neurons requires fast voltage sensitive mechanisms for closing and opening the pore. Anything that interferes with the membrane voltage can alter channel gating and comparatively small changes in the gating properties of a channel can have profound effects. Extremely low frequency electrical or magnetic fields are thought to produce, at most, microvolt changes in neuronal membrane potential. At first sight, such changes in membrane potential seem orders of magnitude too small to significantly influence neuronal signalling. However, in the central nervous system, a number of mechanisms exist which amplify signals. This may allow such small changes in membrane potential to induce significant physiological effects. ...
Mammalian cells are equipped with a large number of ion channels with diverse activation mechanisms and/or modalities. Ion channels are mainly located in the plasma membrane and thus serve crucial molecular mechanisms that transduce extracellular physical, biochemical or biological signals to intracellular events via mediating the movement of ions, particularly Ca2+ entry to elevate the intracellular Ca2+ level. Ion channels are also found in the membrane of intracellular organelles and regulate the ion homeostasis in such intracellular compartments as well as the cytosol. As such, ion channels play an important role in a wide range of physiological processes, which are not restricted to cell excitability. Accumulating evidence show that alterations in the expression and/or function of both the ion-forming or auxiliary subunits occur in neoplastic and malignant cells, markedly influencing cell apoptosis, proliferation, migration and invasion. In addition, ion channels significantly modulate the function
The voltage sensing domain (VSD) of the voltage-gated proton channel Hv1 mediates a H(+)-selective conductance that is coordinately controlled by the membrane potential (V) and the transmembrane pH gradient (ΔpH). Allosteric control of Hv1 channel opening by ΔpH (V-ΔpH coupling) is manifested by a characteristic shift of approximately 40 mV per ΔpH unit in the activation. To further understand the mechanism for V-ΔpH coupling in Hv1, H(+) current kinetics of activation and deactivation in excised membrane patches were analyzed as a function of the membrane potential and the pH in the intracellular side of the membrane (pHI). In this study, it is shown for the first time to our knowledge that the opening of Hv1 is preceded by a voltage-independent transition. A similar process has been proposed to constitute the step involving coupling between the voltage-sensing and pore domains in tetrameric voltage-gated channels. However, for Hv1, the VSD functions as both the voltage sensor and the conduction
Sigma-Aldrichs Cell Signaling & Neuroscience Voltage-Gated Ion Channels. The majority of ion channels fall into two broad categories: voltage-gated ion channels (VGIC) and ligand-gated ion channels (LGIC). Members of the VGIC superfamily are usually closed at the resting potential of the cell.
Most cells are known to respond to mechanical cues, which initiate biochemical signalling pathways and play a role in cell membrane electrodynamics. These cues can be transduced either via direct activation of mechanosensitive (MS) ion channels or through deformation of the cell membrane and cytoskeleton. Investigation of the function and role of these ion channels is a fertile area of research and studies aimed at characterizing and understanding the mechanoactive regions of these channels and how they interact with the cytoskeleton are fundamental to discovering the specific role that mechanical cues play in cells. In this review, we will focus on novel techniques, which use magnetic micro- and nanoparticles coupled to external applied magnetic fields for activating and investigating MS ion channels and cytoskeletal mechanics.
Our work focuses on the molecular mechanisms underlying the robustness of neuronal activity. The properties of ion channels or synapses are dynamically regulated to maintain a stable level of activity, despite numerous external or internal disturbances. This stability depends on the dynamic regulation of various ion channels responsible for neuronal activity. We believe that dynamic processes regulate in a coordinated manner the properties of functionally-overlapping ion channels. We seek to determine the mechanisms responsible for the dynamic regulation of ion channels in the dopaminergic neurons of the substantia nigra pars compacta of rodents. These neurons are able to spontaneously generate regular activity patterns in the absence of any stimuli (including synaptic inputs). This pacemaker property allows us to precisely define their patterns of activity in vitro and to determine the causal relationships between the properties of the voltage-gated ion channels expressed by these neurons and ...
Only a few years ago, in 2011, the Sternson group exploited the properties of specialized domains to engineer new ligand-gated channels, which they called PSAMs2. First, the Sternson group made the critical observation that ligand-gated (i.e. molecule-sensing) ion channels can be divided into two somewhat independent domains, the ligand-binding domain and the ion channel domain. By screening candidate mutations in the ligand-binding domain of a starter channel, they were able to engineer the channel to lose its innate affinity to its natural ligand and acquire a preference for a synthetic molecule. By transplanting this new ligand binding domain onto other excitatory and inhibitory ion channel domains, the Sternson group successfully created novel excitatory and inhibitory channels. These channels now specialize in binding synthetic ligands that have never occurred in any biological system and are used as a tool to manipulate neuron activities.. Recent work by researchers in the Jan labs ...
A transformed line of human embryonic kidney epithelial cells (HEK 293) is commonly used as an expression system for exogenous ion channel genes. Previously, it has been shown that these cells contain mRNAs for a variety of ion channels. Expression of some of these genes has been confirmed at the protein level. Patch-clamp electrophysiology experiments confirm the presence of multiple ion channels and molecular data agree with pharmacological profiles of identified channels. In this work, we show that endogenous voltage-gated potassium channels in HEK cells are a significant source of outward current at positive potentials. We show that both non-transfected HEK cells and HEK cells transfected with hyperpolarization-activated cyclic-nucleotide gated (HCN) channels have a significant amount of voltage-gated potassium (K(V)) current when certain tail current voltage-clamp protocols are used to assay HCN current activation. Specifically, tail current protocols that use a depolarized holding ...
Ion channels are transmembrane proteins that allow ions to move in or out of cells, and they are vital to a range of biological processes. They can be opened and closed in a number of ways: for example, some are opened by voltage, while others respond to the binding of ligands. Piezo1 and Piezo2 are mechanosensitive ion channels: in other words, they open in response to mechanical stimulation, such as stretching or shear stress (Coste et al., 2010, 2012).. Mutations in the gene Piezo1 have been linked to a blood disease called xerocytosis that leads to hemolytic anemia (Albuisson et al., 2013; Bae et al., 2013; Coste et al., 2013; Zarychanski et al., 2013). It is known that these mutations reduce the ability of the Piezo1 ion channel to close, and this leads to red blood cells shrinking as a result of dehydration. However, the details of this process are not fully understood. Now, in a pair of papers in eLife, Ardem Patapoutian, Michael Bandell and colleagues at the Scripps Research Institute, ...
Three synthetic peptides corresponding to transmembrane segments TMS1, TMS3 and TMS6 of secondary-active transporter MntH from Escherichia coli were used as a suitable alternative model enabling to study TMS structure, TMS interaction with membranes, TMS mutual interaction and also function of MntH. The secondary structure of the peptides was estimated in different environments using circular dichroism spectroscopy. These peptides interacted with and adopted helical conformation in lipid membranes. Electrophysiological experiments demonstrated that individual TMS were able under certain conditions to form ion channels in model biological membranes. Electrophysiological properties of these weakly cation-selective ion channels were strongly dependent on surrounding pH. Manganese ion, as a physiological substrate of MntH, enhanced the conductivity of TMS1 and TMS6 channels, influenced the transition between closed and open states and affected the conformation of all studied peptides. For TMS3 Mn2+ ...
Ion channel conformational changes within the lipid membrane are a key requirement to control ion passage. Thus, it seems reasonable to assume that lipid composition should modulate ion channel function. There is increasing evidence that this implicates not just an indirect consequence of the lipid influence on the physical properties of the membrane, but also specific binding of selected lipids to certain protein domains. The result is that channel function and its consequences on excitability, contractility, intracellular signaling or any other process mediated by such channel proteins, could be subjected to modulation by membrane lipids. From this it follows that development, age, diet or diseases that alter lipid composition should also have an influence on those cellular properties. The wealth of data on the non-annular lipid binding sites in potassium channel from Streptomyces lividans (KcsA) makes this protein a good model to study the modulation of ion channel structure and function by lipids.
Ion channels, which allow potassium and sodium ions to flow in and out of cells, are crucial in neuronal firing in the central nervous system and for brain and heart function. These channels use a ball-and-chain mechanism to help regulate their ion flow, according to a new study led by Weill Cornell Medicine scientists.. The study, published March 18, 2020, in Nature, confirms a long-standing hypothesis about ion channels, and represents a key advance in the understanding of the basic biological processes at work in most cells.. The direct imaging of the ball-and-chain mechanism, using electron-microscopy techniques, can also provide a new angle to design drugs that target it to improve ion channel function. Ion channel abnormalities have been linked to a long list of disorders including epilepsies, heart arrhythmias, schizophrenia and diabetes.. Scientists have been trying to get an atomic-scale picture of this mechanism since the 1970s, and now that we have it at last, it can become an ...
Concentration-dependent biphasic effects of drugs on ion channel activity have been reported in a variety of preparations, usually with stimulatory effects seen at low concentrations followed by increasingly dominant inhibition at higher levels. Such behaviour is often interpreted as evidence for the existence of separate modulatory drug binding sites. We demonstrate in this paper that it is possible for biphasic effects to be produced in an allosteric model of a ligand-activated ion channel, where diffusion-limited binding of the modulatory drug is restricted to either a stimulatory or an inhibitory site (but not both) because of steric overlap. The possibility of such an interaction mechanism should be kept in mind when interpreting experimental data if stoichiometric evidence from complementary techniques suggests that only one drug molecule is bound per receptor/ion channel complex.. ...
Voltage-dependent ion channels have been found in the plasma membrane of the yeast Saccharomyces cerevisiae. Ion channel activities were recorded from spheroplasts or patches of plasma membrane with the patch-clamp technique. The most prominent activities came from a set of potassium channels with the properties of activation by positive but not negative voltages, high selectivity for potassium over sodium ion, unit conductance of 20 picosiemens, inhibition by tetraethylammonium or barium ions, and bursting kinetics. ...
Dopaminergic neurons of the substantia nigra pars compacta (SNc) are involved in the control of movement, sleep, reward, learning, and nervous system disorders and disease. To date, a thorough characterization of the ion channel phenotype of this important neuronal population is lacking. Using immunohistochemistry, we analyzed the somatodendritic expression of voltage-gated ion channel subunits that are involved in pacemaking activity in SNc dopaminergic neurons in 6-, 21-, and 40-day-old rats. Our results demonstrate that the same complement of somatodendritic ion channels is present in SNc dopaminergic neurons from P6 to P40. The major developmental changes were an increase in the dendritic range of the immunolabeling for the HCN, T-type calcium, Kv4.3, delayed rectifier, and SK channels. Our study sheds light on the ion channel subunits that contribute to the somatodendritic delayed rectifier (Kv1.3, Kv2.1, Kv3.2, Kv3.3), A-type (Kv4.3) and calcium-activated SK (SK1, SK2, SK3) potassium ...
Neural activity depends on the kinetic properties of ion channels expressed in neurons. Small changes in these properties can dramatically affect synaptic integration, membrane excitability and circuit function. Like all biochemical processes, the kinetics of ion channels have an exponential temperature dependence and the exponent (the Q10) differs several-fold between ion channel types within species [1-3]. In warm-blooded animals such as mammals, deviations in temperature of only a few degrees Celsius can thus disrupt neural activity and lead to loss of consciousness or death. However, cold blooded animals, including all invertebrates, manage to survive and function despite temperature fluctuations of tens of degrees Celsius [1]. How is this robustness achieved? One possibility is that the self-regulating, activity-dependent mechanisms that maintain neuronal properties in cold-blooded animals operate in a way that specifically gives rise to temperature robustness. In this work we develop a ...
To investigate the cellular mechanism responsible for the apical membrane Cl conductance in airway epithelia, we used the patch-clamp technique to study single ion channels in primary cultures of...
Spontaneously opening, chloride-selective channels that showed outward rectification were recorded in ripped-off patches from rat cultured hippocampal neurons and in cell-attached patches from rat hippocampal CA1 pyramidal neurons in slices. In both preparations, channels had multiple conductance states and the most common single-channel conductance varied. In the outside-out patches it ranged from 12 to 70 pS (Vp=40 mV) whereas in the cell-attached patches it ranged from 56 to 85 pS (-Vp=80 mV). Application of GABA to a patch showing spontaneous channel activity evoked a rapid, synchronous activation of channels. During prolonged exposure to either 5 or 100 microM GABA, the open probability of channels decreased. Application of GABA appeared to have no immediate effect on single-channel conductance. Exposure of the patches to 100 microM bicuculline caused a gradual decrease on the single-channel conductance of the spontaneous channels. The time for complete inhibition to take place was slower ...
An input/output data channel operates in conjunction with a virtual memory computer. A channel operation is commenced with the execution of a start I/O instruction which transfers a channel address word (CAW) to the channel. The CAW contains a virtual command address pointing to the beginning of a virtual channel program. The virtual command address is presented to a channel look-aside buffer which translates the virtual command to a real memory address for accessing main storage. The virtual channel command words (CCWs) which comprise the channel program are successively translated by the channel look-aside buffer. A virtual address stack within the buffer holds active virtual data addresses and command addresses for each channel. Interlocking between this stack and a CPU translation mechanism is provided by an I/O bit array. The I/O bit array contains a count mechanism for each memory frame which may be addressed by the channel. Each time a memory frame is addressed by any of the channels, the
Abstract: Muscarinic K1 (KACh) channels are key determinants of the inhibitory synaptic transmission in the heart. These channels are heterotetramers consisting of two homologous subunits G-protein-gated inwardly rectifying K1 (GIRK)1 and GIRK4 and have unitary conductance of ;35 pS with symmetrical 150 mM KCl solutions. Activation of atrial KACh channels however is often accompanied by the appearance of openings with a lower conductance suggesting a functional heterogeneity of G-protein-sensitive ion channels in the heart. Here we report the characterization of a small conductance GIRK (scGIRK) channel present in rat atria. This channel is directly activated by Gbg subunits and has a unitary conductance of 16 pS. The cGIRK and KACh channels display similar affinities for Gbg binding and are frequently found in the same membrane patches. Furthermore Gbg-activated scGIRK channelsâ€like their KACh counterpartsâ€exhibit complex gating behavior fluctuating among four functional modes ...
Neurons are highly polarized cells with apparent functional and morphological differences between dendrites and axon. A critical determinant for the molecular and functional identity of axonal and dendritic segments is the restricted expression of voltage-gated ion channels. Several studies show an uneven distribution of ion channels and their differential regulation within dendrites and axons, which is a prerequisite for an appropriate integration of synaptic inputs and the generation of adequate action potential firing patterns. This review will focus on the signaling pathways leading to segmented expression of voltage-gated potassium and sodium ion channels at the neuronal plasma membrane and the regulatory mechanisms ensuring segregated functions. We will also discuss the relevance of proper ion channel targeting for neuronal physiology and how alterations in polarized distribution contribute to neuronal pathology.
Trimeric intracellular cation-selective (TRIC) channel subtypes, namely TRIC-A and TRIC-B, are derived from distinct genes and distributed throughout the sarco/endoplasmic reticulum (SR/ER) and nuclear membranes. TRIC-A is preferentially expressed at high levels in excitable tissues, while TRIC-B is ubiquitously detected at relatively low levels in various tissues. TRIC channels are composed of ~300 amino acid residues and contain three putative membrane-spanning segments to form a bullet-shaped homo-trimeric assembly. Both native and purified recombinant TRIC subtypes form functional monovalent cation-selective channels in a lipid bilayer reconstitution system. The electrophysiological data indicate that TRIC channels behave as K(+) channels under intracellular conditions, although the detailed channel characteristics remain to be investigated. The pathophysiological defects detected in knockout mice suggest that TRIC channels support SR/ER Ca(2+) release mediated by ryanodine (RyR) and inositol
Patch clamp method was used to search for, and characterize ion channel activity which may participate in cation influx in human myeloid K562 cells. In cell-attached, outside-out and whole-cell experiments two types of voltage-insensitive Na-permeable channels were identified with different selectivities for monovalent cations, referred to as channels of high (HS) and low (LS) selectivity. The unitary conductance was similar for both channel types being 12 pS (145 mmol/l Na, 23 degrees C). The relative permeability PNa/PK estimated from the extrapolated reversal potential values were 10 and 3 for HS and LS channels, respectively. Both HS and LS channels were found to be impermeable to bivalent cations (Ca2+ or Ba2+). The activity of HS and LS channels displayed a tendency to increase with depolarization. Both channel types were not blocked by tetrodotoxin and were insensitive to amiloride in the concentration range of up to 100 mumol/l. At higher concentrations (0.1-2 mmol/l), amiloride ...
The invention relates to the field of drug delivery, in particular, to compounds and methods for the chemical modification of a proteinaceous channel to be used in pharmaceutical delivery vehicles for controlled and/or localized release of therapeutic molecules (e.g., small molecules, peptides, proteins or other macromolecules). Provided are pH- and/or light-responsive compounds capable of controlling the channel activity of a mechanosensitive channel, such as the MscL channel protein of E. coli, or a functional equivalent thereof, and use of these compounds to convert a mechanosensitive channel protein into a pH- and/or light-responsive channel. Also provided are drug delivery vehicles comprising a pH- and/or light-responsive channel protein.
BK channels regulate vascular tone by hyperpolarizing smooth muscle in response to fluctuating calcium concentrations. Oestrogen has been reported to lower blood pressure by increasing BK channel open probability through direct binding to the regulatory beta1-subunit(s) associated with the channel. The present investigation demonstrates that 17beta-oestradiol activates the BK channel complex by increasing the burst duration of channel openings. A subconductance state was observed in 25% of recordings following the addition of 17beta-oestradiol and could reflect uncoupling between the pore forming alpha1-subunit and the regulatory beta1-subunit. We also present evidence that more than one beta1-subunit is required to facilitate binding of 17beta-oestradiol to the channel complex.
Typically the activities of the ion channels are not called firing patterns as in neuroscience we refer to firing when we mean the elicitation of action potentials (spikes) but yes: Whenever an AP was fired a sufficient amount of sodium channels had to be open and therefore I thing your reasoning is correct. In other terms what you are saying is that the effective channel conductances change during an action potential.. On your conclusion: In the regime of natural parameters the time scale of firing pattern 1 mostly depends on the time constants of the voltage gated ion channels and not so much on the absolute number of channels (especially if all the conductances would scale equally). In the world of Hodgin-Huxley like coupled- and nonlinear-dynamical systems the voltage does not scale strictly linear with increasing the participating max. conductances. The interplay of max. conductance and temporal gating dynamics resulting in the effective conductance itself depends on the voltage and there ...
Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes an alpha-1 subunit of a voltage-dependent calcium channel. Calcium channels mediate the influx of calcium ions into the cell upon membrane polarization. The alpha-1 subunit consists of 24 transmembrane segments and forms the pore through which ions pass into the cell. The calcium channel consists of a complex of alpha-1, alpha-2/delta, beta, and gamma subunits in a 1:1:1:1 ratio. There are multiple isoforms of each of these proteins, either encoded by different genes or the result of alternative splicing of transcripts. The protein encoded by this gene binds to and is inhibited by dihydropyridine. Alternative splicing results in many transcript variants encoding different proteins. Some of the predicted proteins may not produce functional ion channel subunits. [provided by RefSeq, Oct 2012 ...
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This study reports the formation of self-assembled transmembrane anion channels by small-molecule fumaramides. Such artificial ion channel formation was confirmed by ion transport across liposomes and by planar bilayer conductance measurements. The geometry-optimized model of the channel and Cl− ion selectivity wit
Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain and the central nervous system, but also in the cardiovascular system. Prevents aberrant action potential firing and regulates neuronal output. Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane (PubMed:12527813, PubMed:21233214). Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNA1, KCNA2, KCNA4, KCNA5, KCNA6, KCNA7, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel (PubMed:20696761). Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location of the alpha subunits and promote rapid inactivation of
Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain and the central nervous system, but also in the cardiovascular system. Prevents aberrant action potential firing and regulates neuronal output. Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane (PubMed:19912772, PubMed:8495559, PubMed:11211111, PubMed:23769686). Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNA1, KCNA2, KCNA4, KCNA5, KCNA6, KCNA7, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel (PubMed:8495559, PubMed:20220134). Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location ...
Glutamate activates a number of different receptor-channel complexes, each of which may contribute to generation of excitatory postsynaptic potentials in the mammalian central nervous system. The rapid application of the selective glutamate agonist, quisqualate, activates a large rapidly inactivating current (3 to 8 milliseconds), which is mediated by a neuronal ionic channel with high unitary conductance (35 picosiemens). The current through this channel shows pharmacologic characteristics similar to those observed for the fast excitatory postsynaptic current (EPSC); it reverses near 0 millivolts and shows no significant voltage dependence. The amplitude of the current through this channel is many times larger than that through the other non-NMDA (N-methyl-D-aspartate) channels. These results suggest that this high-conductance quisqualate-activated channel may mediate the fast EPSC in the mammalian central nervous system. ...
Changes of the electrical charges across the surface cell membrane are absolutely necessary to maintain cellular homeostasis in physiological as well as in pathological conditions. The opening of ion channels alter the charge distribution across the surface membrane as they allow the diffusion of ions such as K+, Ca++, Cl−, Na+. Traditionally, voltage-gated ion channels (VGIC) are known to play fundamental roles in controlling rapid bioelectrical signaling including action potential and/or contraction. However, several investigations have revealed that these classes of proteins can also contribute significantly to cell mitotic biochemical signaling, cell cycle progression, as well as cell volume regulation. All these functions are critically important for cancer cell proliferation. Interestingly, a variety of distinct VGICs are expressed in different cancer cell types, including metastasis but not in the tissues from which these tumors were generated. Given the increasing evidence suggesting ...
Erwin Neher and Bert Sakmann developed a technique which allows the minute currents that flow through the ion channels of cell membranes to be amplified and recorded.
Plant growth depends on the maintenance of the adequate intracellular levels of potassium ion (K+). Different abiotic stresses threaten this homeostasis, thus, the characterization of the molecules involved in the regulation of cytoplasmic K+ concentration is important as they could be targeted for plant crop improvement. The families of 10 Calcineurin B like (CBL) calcium sensors and 26 CBL-Interacting Protein Kinases (CIPK) decode the calcium signals elicited by stress and regulate different ion channels and transporters involved in the control of K+ fluxes in plants. Nevertheless, the detailed molecular mechanisms balancing specificity and versatility to the system require investigation. Here, we show that the cytosolic domain of t he inwardrectifier K+ channel (AKT1) harbors a non-canonical ankyrin domain which is not essential for channel function but serves as a docking site for its regulator, the CIPK23 protein kinase. Mutations on this domain impair kinase channel association. This ...
Nanion offers analysis instruments for ion channel analysis, as patch clamp, impedance and bilayer recordings, used for drug development as cardiac safety and basic research.
The cell membranes of all organisms contain ion channels that permit ions to pass into or out of the cell, and these channels play extremely important roles in fundamental physiological processes such as heartbeats and the rapid conduction of signals along neurons. An important property of these ion channels is their selective conductivity-they selectively permit the passage of particular ions. For example, potassium channels more readily permit the passage of potassium ions than the passage of sodium ions, despite the fact that potassium ions are larger.
The PMX multi channel data acquisition system can be used to measure and control in real-time. This system is ideal for production and quality assurance.
TY - JOUR. T1 - Inhibition of ligand-gated cation-selective channels by tamoxifen. AU - Allen, Marcus. AU - Newland, Claire. AU - Valverde, Miguel A.. AU - Hardy, Simon. PY - 1998/9/16. Y1 - 1998/9/16. U2 - 10.1016/S0014-2999(98)00454-3. DO - 10.1016/S0014-2999(98)00454-3. M3 - Article. VL - 354. SP - 261. EP - 269. JO - European Journal of Pharmacology. JF - European Journal of Pharmacology. SN - 0014-2999. IS - 2-3. ER - ...
Ligand-gated ion channels (LGICs) are a group of transmembrane ion channel proteins which open to allow ions such as Na+, K+, Ca2+, or Cl- t ...
K+ selective channels are some of the most widespread ion trafficking molecules in living organisms, with more than 70 genes encoding different K+ channels in humans. KV channels fall into one of the two classical categories of delayed rectifier (DR) and A-type. Delayed rectifier was the original name attributed to voltage-dependent K+ channels due to their delayed activation in squid giant axons. A-type channels are low voltage-activated, fast inactivating (therefore, transient) K+ channels. Specific KV toxins are often used to dissect the particular contribution of different subunits to native currents.. Alomone Labs is excited to offer a line of Overexpressed Membrane Fractions. These membrane fractions are Xenopus oocyte membrane lysates overexpressing a specific ion channel. Fractions are sold as a set of injected and non-injected oocytes and can be used as controls for Alomone Labs antibodies. Overexpressed Membrane Fractions can also be purchased as a kit with their respective antibody. ...
What is difference between Ion Channel and Transporter? Ion channel involves in passive transportation of ions while, transporter involves active transportation
TY - JOUR. T1 - Kv2.1 channels play opposing roles in regulating membrane potential, Ca2+ channel function, and myogenic tone in arterial smooth muscle. AU - ODwyer, Samantha C.. AU - Palacio, Stephanie. AU - Matsumoto, Collin. AU - Guarina, Laura. AU - Klug, Nicholas R.. AU - Tajada, Sendoa. AU - Rosati, Barbara. AU - McKinnon, David. AU - Trimmer, James S.. AU - Santana, L. Fernando. PY - 2020/2/18. Y1 - 2020/2/18. N2 - The accepted role of the protein Kv2.1 in arterial smooth muscle cells is to form K+ channels in the sarcolemma. Opening of Kv2.1 channels causes membrane hyperpolarization, which decreases the activity of L-type CaV1.2 channels, lowering intracellular Ca2+ ([Ca2+]i) and causing smooth muscle relaxation. A limitation of this model is that it is based exclusively on data from male arterial myocytes. Here, we used a combination of electrophysiology as well as imaging approaches to investigate the role of Kv2.1 channels in male and female arterial myocytes. We confirmed that ...
It has long been known that there is a rapid ion exchange over the cell membrane, but Neher and Sakmann were the first to show that specific ion channels actually exist. To elucidate how an ion channel operates it is necessary to be able to record how the channel opens and closes. This appeared elusive since the ionic current through a single ion channel is extraordinarily small. In addition, the small ion channel molecules are embedded in the cell membrane. Neher and Sakmann succeeded in solving these difficulties. They developed a thin glass micropipette (a thousandths of a millimeter in diameter) as a recording electrode. When it is brought in contact with the cell membrane, it will form a tight seal with the periphery of the pipette orifice (Figure 1A, B). As a consequence the exchange of ions between the inside of the pipette and the outside can only occur through the ion channel in the membrane fragment (Figure 1B). When a single ion channel opens, ions will move through the channel as an ...
Proper expression of ion channel genes is responsible for maintaining the electrical properties of cardiac tissue. Ion channel expression changes across different areas of the heart. These changes allow myocytes to specialize in signal propagation, contraction, or pace-making. Further alterations in ion channel transcriptional expression are associated with diseases such as atrial fibrillation. We study the regulation of ion channel gene expression at the transcriptional level using bioinformatic data mining approaches to analyze the core promoter of ion channel genes. Our efforts to predict ion channel expression patterns may lead to novel drug targets in treating cardiovascular arrhythmias and disease.. We have developed a bioinformatic method of identifying short stretches of DNA sequence that may be responsible for differences in gene expression of one group compared to a background group. Our method involves identifying all motifs conserved in the DNA of any promoter sequence and ...
Cyclic nucleotide-gated (CNG)1 ion channels are key players in visual and olfactory signal transduction pathways (reviewed in Lancet, 1986; Yau and Baylor, 1989; Zufall et al., 1994). Although they are only weakly voltage dependent, CNG channels have regions of sequence similarity with voltage-gated channels (Jan and Jan, 1990). One region of high conservation between CNG channels and voltage-gated channels is the P region, thought to line a portion of the ion-conducting pore. Shaker K+ channels that have had portions of their P region replaced with the corresponding region from CNG channels take on many of the permeation properties of CNG channels (Heginbotham et al., 1992). These chimeric channels become permeable to Na+ as well as to K+ and become blocked by the divalent cations Mg2+ and Ca2+. Like voltage-gated channels, CNG channels are thought to possess multi-ion pores (Furman and Tanaka, 1990; Sesti et al., 1995). The external divalent cation binding site is thought to involve the E363 ...
Nicotinic acid adenine dinucleotide phosphate (NAADP) is a potent Ca2+-releasing second messenger that might regulate different ion channels, including the ryanodine receptor, two-pore channels, and TRP-ML1 (transient receptor potential channel, subtype mucolipin 1), a Ca2+ channel localized to lysosomes. New evidence suggests that a 22- and 23-kilodalton pair of proteins could be the receptor for NAADP. Labeling of NAADP binding proteins was independent of overexpression or knockout of two-pore channels, indicating that two-pore channels, although regulated by NAADP, are not the NAADP receptors. I propose that NAADP binding proteins could bind to different ion channels and thus may explain how NAADP regulates diverse ion channels.. ...
TY - JOUR. T1 - Compound-induced block of ion channel pore function. T2 - Inward-rectifier potassium channels as a model. AU - Furutani, Kazuharu. AU - Hibino, Hiroshi. AU - Inanobe, Atsushi. AU - Kurachi, Yoshihisa. PY - 2009/12/1. Y1 - 2009/12/1. N2 - Small chemical compounds modulate ion channel functions. This is the reflection of ligand interactions with ion channels at their various sites. Many biophysical and biochemical researches have been performed on this subject and have provided important basic concepts on the structure-functional relationships of ion channels. Especially, ion channel blockers have been excellent tools for biophysical studies of ion channels and some of them are actually used for treating various diseases. The mechanisms underlying the blocking action of various chemical compounds, however, remain largely unknown at the atomic level, partly because of the promiscuous nature of the reaction. As one of the attempts to overcome the problem, we have adopted a novel ...
My dissertation work has focused on identifying regulatory mechanisms that govern Cyclic Guanosine Monophosphate (cGMP)-activation of Aquaprorin-1 (Aqp1) ion channels. Aquaporins serve as pores for water thus allowing enhanced water permeability in biological membranes (Preston, et al., 1992). A subset of Aquaporin proteins behave as ion channels regulated by intracellular signaling pathways (Anthony, et al., 2000; Ehring, et al., 1990; Yasui, et al., 1999a). cGMP is necessary for Aqp1 ion channel activation, but only a small subpopulation of Aqp1 proteins function as cGMP-activated ion channels . This observation indicates the involvement of additional regulatory mechanisms in the gating Aqp1 ion channels. Work from this dissertation provides the first insight into the potential mechanism that dictates Aqp1 ion channel availability to respond to the cGMP signal. I show here that insulin-activated tyrosine kinases positively regulate cGMP-mediated activation of Aqp1 ion channels when expressed ...
It is clear that the voltage--‐gated proton channel HVCN1 plays an essential role in a range of cell types, in particular immune cells. Previous published work has confirmed the existence of proton channels in both murine and human macrophages. However, the role of HVCN1 in macrophages has not been investigated. Given that the current literature on voltage--‐gated proton channels in immune cells has found HVCN1 to be involved in several cellular processes (such as the respiratory burst and signalling events) it is important to establish its functional role in macrophages, which are a crucial constituent of the immune system. The aim of my thesis was to investigate the function of voltage--‐gated proton channels in macrophages with the use of mice with a disrupting mutation within the Hvcn1 gene, which results in HVCN1 loss. In particular, I wanted to address how Hvcn1--‐/--‐ macrophages responded to LPS activation. I hypothesised that HVCN1 regulates the respiratory burst of ...
Ca2+ signaling is central to many aspects of plant physiology; however, the channels involved in mediating Ca2+ fluxes in plants remain largely elusive. This is at least partially due to the absence of plant homologs to many of the well-characterized Ca2+ channels present in animals. Instead, plants have expanded families of ligand-gated, non-specific cation channels such as the cyclic nucleotide-gated channels (CNGCs) and glutamate receptor-like channels (GLRs), which are hypothesized to provide Ca2+ channel function in plants. The 20 member CNGC family represents one of two large families of putative Ca2+ channels in Arabidopsis, and various isoforms have been implicated in plant development and stress-response signaling, including immunity. Among Arabidopsis CNGC mutants, cpr22 and dnd1 are the best characterized mutants that show similar autoimmunity phenotypes such as constitutive expression of PR genes and heightened accumulation of salicylic acid. To understand the regulation of plant ...
Chloride channels are a superfamily of poorly understood ion channels specific for chloride. These channels may conduct many different ions, but are named for chloride because its concentration in vivo is much higher than other anions. Several families of voltage-gated channels and ligand-gated channels (e.g., the CaCC families) have been characterized in humans. Voltage-gated chloride channels display a variety of important physiological and cellular roles that include regulation of pH, volume homeostasis, organic solute transport, cell migration, cell proliferation and differentiation. Based on sequence homology the chloride channels can be subdivided into a number of groups. Voltage-gated chloride channels are important for setting cell resting membrane potential and maintaining proper cell volume. These channels conduct Cl− as well as other anions such as HCO− 3, I−, SCN−, and NO− 3. The structure of these channels are not like other known channels. The chloride channel subunits ...
Ion channels are proteins that traverse the cell membrane and form gated pores that open and close in response to various stimuli. In order to experimentally probe aspects of ion channel functionality, we performed subtle structure function studies using the in vivo nonsense suppression method, which allows for the incorporation of synthetically accessible unnatural amino acids and hydroxy acids into an ion channel at a site of interest. Fluorinated aromatic amino acids are good probes for a cation-π interaction because fluorine substituents reduce the binding affinity of the aromatic for a cation in a linear, step-wise fashion. In collaboration with Professor Richard Horn at the Thomas Jefferson University, we substituted a series of fluorinated phenylalanines for important tyrosines in the Shaker B K+ channel and experimentally determined that TEA was binding to the residues through a cation-π interaction. We also determined that Ca2+ binds to and blocks the NaV1.4 channel through a ...
Alamethicin forms voltage-gated ion channels that have moderate cation-selectivity. The enhancement of the cation-selectivity by introducing negatively charged residues at positions 7 and 18 has been studied using the tethered homodimers of alamethicin with Q7 and E18 (di-alm-Q7E18) and its analog with E7 and Q18 (di-alm-E7Q18). In the dimeric peptides, monomer peptides are linked at the N-termini by a disulfide bond. Both the peptides formed long lasting ion channels at cis-positive voltages when added to the cis-side membrane. Their long open duration enabled us to obtain current-voltage (I-V(m)) relations and reversal potentials at the single-channel level by applying a voltage ramp during the channel opening. The reversal potentials measured in asymmetric KCl solutions indicated that ionized E7 provided strong cation-selectivity, whereas ionized E18 little influenced the charge selectivity. This was also the case for the macroscopic charge selectivity determined from the reversal potentials obtained
Voltage-gated ion channels generate electrical activity in excitable cells. As such, they are essential components of neuromuscular and neuronal systems, and are targeted by toxins from a wide variety of phyla, including the cnidarians. Here, we review cnidarian toxins known to target voltage-gated ion channels, the specific channel types targeted, and, where known, the sites of action of cnidarian toxins on different channels.
Statistical inference is considered for a two-state Markov model of a single ion channel, when time interval omission is incorporated. A simple method of obtaining confidence sets for the mean open and closed sojourn times for the underlying single channel, based on the method-of-moments estimators, is presented. Time interval omission induces non-identifiability, in that the method-of-moments usually leads to two distinct estimates of the mean open and closed sojourn times, one corresponding to the true values and the other being an artefact of time interval omission. A new method of overcoming such non-identifiability on the basis of one single channel record is described. The methodology is illustrated by a numerical example. ...
Cyclic peptides are ring structures that consist of alternating L-and D amino acids. In this thesis, CP 5-10 (six cyclic peptides synthesized by Dr. Juan R. Granja, University of Santiago, Spain, and colleagues) were shown to support Na+ flux in black lipid membranes (BLM) with conductances ranging from 33 to 667 pS. CPs ability to form active ion channels was confirmed with 23Na NMR. The previously proposed mechanism of cyclic peptide ion channel formation was that 6 to 10 flat CP rings stack on top of each other, perpendicular to the phospholipid bilayer (Hartgerink et al., 1995). However, CP-6 and CP-8 are strong dimers that can also function as ion channels as demonstrated in our BLM and 23Na NMR experiments. Therefore, we hypothesized that a dimer of the CPs associating across the membrane was sufficient to form an active ion channel. Our investigations were based on the concentration response of the membrane resistance in BLM. With this approach we were able to confirm the dimeric nature of
A novel and improved method for implementing a high-transmission-rate over-the-air interface is described. A transmit system provides an in-phase channel set and a quadrature-phase channel set. The in-phase channel set is used to provide a complete set of orthogonal medium rate control and traffic channels. The quadrature-phase channel set is used to provide a high-rate supplemental channel and an extended set of medium rate channels that are orthogonal to each other and the original medium rate channels. The high-rate supplemental channel is generated over a set of medium rate channels using a short channel code. The medium rate channel are generated using a set of long channel codes.
Pathogenicity and virulence are multifactorial traits, depending on interaction of viruses with susceptible cells and organisms. The ion channels coded by viruses, viroporins, represent only one factor taking part in the cascade of interactions between virus and cell, leading to the entry of virus, replication and to profound changes in membrane permeability. The M2 protein from influenza A virus forms proton-selective, pH-regulated channel involved in regulating vesicular pH, a function important for the correct maturation of HA glycoprotein. The NB glycoprotein of influenza B viruses is an integral membrane protein with an ion channel activity. The CM2 protein of influenza C virus is an integral membrane glycoprotein structurally analogous to influenza A virus M2 and influenza B virus NB proteins. The picornavirus 3A protein is involved in cell lysis and shows homology with other lytic proteins. Vpu is an oligomeric integral membrane protein encoded by HIV-1, which forms ion channels. The ...
An increasing number of studies show that the activation of the innate immune system and inflammatory mechanisms play an important role in the pathogenesis of numerous diseases. The innate immune system is present in almost all multicellular organisms and its activation occurs in response to pathogens or tissue injury via pattern-recognition receptors (PRRs) that recognize pathogen-associated molecular patterns (PAMPs) or danger-associated molecular patterns (DAMPs). Intracellular pathways, linking immune and inflammatory response to ion channel expression and function, have been recently identified. Among ion channels, the transient receptor potential (TRP) channels are a major family of non-selective cation-permeable channels that function as polymodal cellular sensors involved in many physiological and pathological processes. In this review, we summarize current knowledge of interactions between immune cells and PRRs and ion channels of TRP families with PAMPs and DAMPs to provide new insights into
Corfas G., Fischbach G.D.. ARIA is a glycoprotein purified from chick brain on the basis of its ACh receptor-inducing activity (ARIA). In this study we present evidence that ARIA increases the number of voltage-gated sodium channels in chick muscle as well as the number of ACh receptors (AChRs). Exposure of chick myotubes to ARIA increased by twofold the number of 3H-saxitoxin binding, an effect that is comparable to the increase of AChRs assayed by 125I-alpha-bungarotoxin (125I-alpha-BTX) binding. We also documented effects of ARIA on myoblasts: the number of 125I-alpha-BTX binding sites in the mononucleated muscle cells was increased by 1.5-fold, and the peak TTX-sensitive inward currents increased by the same amount. No change was detected in the voltage dependence of channel activation, in mean channel current, or in mean channel open time. Thus, the Na+ channel is the first molecule, other than AChR subunits, whose expression has been shown to be induced by ARIA. Since sodium channels are ...
Signal transduction, the process by which an extracellular signal is translated into an intracellular message, underlies all brain function. This thesis examines the role of protein phosphorylation in mediating three different molecular mechanisms by which neurotransmitter receptors transduce their signals: chemically-gated ion channels, receptor-linked ion channels and receptor-linked ion pumps. The nicotinic acetylcholine receptor, a neurotransmitter-gated ion channel, is phosphorylated by a protein tyrosine kinase in postsynaptic membranes in vitro and in vivo. Purified nicotinic receptor molecules from Torpedo electroplaques can be phosphorylated to known stoichiometries and reconstituted into lipid vesicles. Tyrosine phosphorylation increases the rate of the rapid phase of desensitization of the receptor as measured by single channel recording but does not alter other channel properties. These data provide direct evidence for the regulation of ion channel properties by tyrosine phosphorylation and
The localization of ion channels to caveolae may modulate the function of the channels in multiple ways. For example, the precise lipid composition can potently regulate channel function, and dynamic changes in this composition underlie some forms of regulation. In addition, the caveolar localization of ion channels can provide compartmentalization of signaling networks, enabling rapid and specific regulation of the channels. Caveolar-localized signaling complexes composed of β2-AR, AC, Gαs, and Gαi have previously been observed in rat ventricular myocytes (9, 19), but the present study adds Cav1.2 and PP2A to the complex. Conversely, the molecules associated with Cav1.2 channels in the heart have not been extensively defined. Recent studies have identified AKAP15 and PKA as well as certain PKC isoforms in association with Cav1.2 in cardiac muscle (23, 24); however, whether these molecules are associated with the channels in caveolae is unknown. The present results add to the list of proteins ...
Currently, we are studying three types of ion channels, i.e., potassium channels, the cGMP-gated cation channel, and the cystic fibrosis conductance regulator chloride channel. Using a combined structural and functional approach, we investigate the mechanisms underlying the ability of potassium channels to perform various important biological tasks, such as generating action potentials, modulating the communications between neurons, controlling the rate of the cardiac pacemaker, and coupling the blood glucose level to insulin secretion. We also examine the mechanisms that enable the cGMP-gated channel to mediate visual photo-transduction in the eye. Recently, we have ventured into the area of how phospholipases regulate ion channel function, a venture that has provided us with new insight into the pathogenesis of cystic fibrosis. Another area of our research is to develop novel protein inhibitors for various types of biologically important ion channels through both passive screening and active ...
Cells dont let just anything slip past their external membranes. Instead, protein channels control the passage of most substances, including the ions that allow nerves to signal, muscles to flex, and hormones to be secreted in an orderly way. For more than a century, chemists have understood that the flow of ions across membranes could produce electrical signals. But exactly how ion channels work has become clear only since 1998, when Roderick MacKinnon, M.D., showed for the first time what these proteins look like at the atomic level. This was such a fundamental achievement that he received the Nobel Prize in chemistry just five years later.. MacKinnon has now solved several riddles about the way ion channels operate, such as how they so precisely limit the types of ions that pass through, why they sometimes conduct ions in one direction only, and how these cellular gates open and shut under different conditions. To answer these questions, MacKinnon has trapped ion channel structures in ...
Voltage-gated n-type K(V) and Ca(2+)-activated K+ [K(Ca)] channels were studied in cell-attached patches of activated human T lymphocytes. The single-channel conductance of the K(V) channel near the resting membrane potential (Vm) was 10 pS with low K+ solution in the pipette, and 33 pS with high K+ solution in the pipette. With high K+ pipette solution, the channel showed inward rectification at positive potentials. K(V) channels in cell-attached patches of T lymphocytes inactivated more slowly than K(V) channels in the whole-cell configuration. In intact cells, steady state inactivation at the resting membrane potential was incomplete, and the threshold for activation was close to Vm. This indicates that the K(V) channel is active in the physiological Vm range. An accurate, quantitative measure for Vm was obtained from the reversal potential of the K(V) current evoked by ramp stimulation in cell-attached patches, with high K+ solution in the pipette. This method yielded an average resting Vm ...
A large percentage of pharmaceutical drugs target ion channels, which are proteins found in a cells membrane, that play a pivotal role in these serious disorders and that are used to test the effectiveness of new drugs.. Ion channels create tiny openings in the membrane for specific ions (atoms that are positively or negatively charged) to pass through. Currently researchers use electrophysiology, which measures an electric current through ion channel proteins, to evaluate the effectiveness of drugs on ion channels.. However, this can be a slow and expensive process as it is typically carried out using ion channels in living cell membranes and producing too many channels can actually kill the cells.. Now, Southampton researchers have been able to produce an ion channel without using cells, which is possible with so-called cell-free expression mixtures, and to insert the channels in a stable artificial cell membrane which should enable faster, less expensive drug testing. The key is that the ...
An interactive system is provided in which information is displayed in response to the entry of the digits of a channel number. The interactive system may be implemented on a television, a computer, or a radio system. The displayed information may be program listings information such as the channel designator or the program currently airing on the channel. The displayed information may also be a list of channels. The list of channels may be associated with the entered digits, may be component channels, or channels of the same type and may be sorted by various techniques such as numerically, by favorite channels, by type, etc. The interactive system may allow a user to specify a source identifier to channels from different sources and display the channels with the source identifier when they are entered.
Gramicidins bactericidal activity is a result of increasing the permeability of the bacterial cell wall allowing inorganic monovalent cations (e.g. H+) to travel through unrestricted, thereby destroying the ion gradient between the cytoplasm and the extracellular environment. That gramicidin D functions as a channel was demonstrated by Hladky and Haydon, who investigated the unit conductance channel. In general, gramicidin channels are ideally selective for monovalent cations and the single-channel conductances for the alkali cations are ranked in the same order as the aqueous mobilities of these ions. Divalent cations like Ca-2+ block the channel by binding near the mouth of the channel. So it is basically impermeable to divalent cations. It also excludes anions. Cl- in particular is excluded from the channel because its hydration shell is thermodynamically stronger than that of most monovalent cations. The channel is permeable to most monovalent cations, which move through the channel in ...
The present study evaluated the contribution of cGMP-dependent versus cGMP-independent pathways in mediating the effects NO on K+ channel activity and vascular tone in renal arterioles. The results indicate that NO selectively enhances the NPo of a large-conductance (195±9 pS) K+ channel in renal VSM cells in a concentration-dependent manner. NO had no significant effect on the activity of the two smaller conductance channels in renal VSM cells that were previously identified as a small-conductance, apamin-sensitive, KCa channel33 and the 4-aminopyridine-sensitive delayed rectifier channel.28 34 35 36 The K+ channel activated by NO is voltage-sensitive and is blocked by TEA and iberiotoxin which are selective inhibitors of the KCa channel.37 38 39 Thus, the present findings indicate that NO activates KCa channels in renal VSM cells, and they are consistent with the results of recent studies with smooth muscle cells isolated from other tissues.6 7 9 11 13 15 Additional experiments were performed ...
The function of nerve and muscle cells relies on ionic currents flowing through ion channels. These ion channels play a major role in cell physiology. One way to investigate ion channels is to use patch clamping. This method allows investigation of ion channels in detail and recording of the electric activity of different types of cells, mainly excitable cells like neurons, muscle fibres or beta cells of the pancreas. The patch clamping technique was developed by Erwin Neher and Bert Sakmann in the 1970s and 80s to study individual ion channels in living cells. In 1991 they received the Nobel Prize for Physiology and Medicine for their work. Today the patch clamping technique is one of the most important methods in the field of electrophysiology. ...
The function of nerve and muscle cells relies on ionic currents flowing through ion channels. These ion channels play a major role in cell physiology. One way to investigate ion channels is to use patch clamping. This method allows investigation of ion channels in detail and recording of the electric activity of different types of cells, mainly excitable cells like neurons, muscle fibres or beta cells of the pancreas. The patch clamping technique was developed by Erwin Neher and Bert Sakmann in the 1970s and 80s to study individual ion channels in living cells. In 1991 they received the Nobel Prize for Physiology and Medicine for their work. Today the patch clamping technique is one of the most important methods in the field of electrophysiology ...
Potassium (K+) channels are found in cell membranes throughout all domains of life. They are important for essential cellular functions including the regulation of cell volume, growth, membrane excitability and K+ secretion and recycling. Among the functionally diverse K+ channels, inwardly rectifying (Kir) channels are unusual in that they preferentially conduct K+ from the extracellular compartment into the cell. Channel subunits are comprised of two transmembrane domains (M1 and M2) flanking a central pore domain (P), which is highly conserved among the great variety of K+ channels. Their presence in prokaryotes and a variety of eukaroytic cell types emphasizes their importance to cells. The mechanisms of permeation, selectivity and rectification are known from the structural analysis of K+ channels in prokaryotes (Doyle et al., 1998; Jiang et al., 2002; Kuo et al., 2003; Nishida et al., 2007) and in mice (Nishida and MacKinnon, 2002). Knowledge of how membrane conduction properties changed ...
In neuroscience, ball and chain inactivation is a model to explain the fast inactivation mechanism of voltage-gated ion channels. The process is also called hinged-lid inactivation or N-type inactivation. A voltage-gated ion channel can be in three states: open, closed, or inactivated. The inactivated state is mainly achieved through fast inactivation, by which a channel transitions rapidly from an open to an inactivated state. The model proposes that the inactivated state, which is stable and non-conducting, is caused by the physical blockage of the pore. The blockage is caused by a ball of amino acids connected to the main protein by a string of residues on the cytoplasmic side of the membrane. The ball enters the open channel and binds to the hydrophobic inner vestibule within the channel. This blockage causes inactivation of the channel by stopping the flow of ions. This phenomenon has mainly been studied in potassium channels and sodium channels. The initial evidence for a ball and chain ...
It plots for me Hodgkin-Huxley activation and inactivation curves. A little explanation: The Hodgkin-Huxley formalism is a way to describe how neurons transmit signals. Neurons transmit signals by electric impulses. There is always a voltage difference between the interior and the exterior of the cell(called membrane potential). If i change this potential somewhere, this temporary change will spread across the cells surface, like a wave. The mechanisms responsible for this process are molecules in the cell membrane(called ion channels), which can open to let ions flow trough, which causes change in the membrane potential. There are tons of different ion channels, but most of them can be described with the Hodgkin-Huxley formalism. These curves describe how much will be these channels open ( 0-closed; 1-fully open) at different membrane potential values. To make things more complicated each ion channel is modeled by 2 curves (activation and inactivation) and the product at a current membrane ...
It plots for me Hodgkin-Huxley activation and inactivation curves. A little explanation: The Hodgkin-Huxley formalism is a way to describe how neurons transmit signals. Neurons transmit signals by electric impulses. There is always a voltage difference between the interior and the exterior of the cell(called membrane potential). If i change this potential somewhere, this temporary change will spread across the cells surface, like a wave. The mechanisms responsible for this process are molecules in the cell membrane(called ion channels), which can open to let ions flow trough, which causes change in the membrane potential. There are tons of different ion channels, but most of them can be described with the Hodgkin-Huxley formalism. These curves describe how much will be these channels open ( 0-closed; 1-fully open) at different membrane potential values. To make things more complicated each ion channel is modeled by 2 curves (activation and inactivation) and the product at a current membrane ...
Ion channels are involved in a broad range of physiological and pathological processes. The implications of ion channels in a variety of diseases, including diabetes, epilepsy, hypertension, cancer and even chronic pain, have signaled them as pivotal drug targets. Thus far, drugs targeting ion channels were developed without detailed knowledge of the molecular interactions between the lead compounds and the target channels. In recent years, however, the emergence of high-resolution structures for a plethora of ion channels paves the way for computer-assisted drug design. Currently, available functional and structural data provide an attractive platform to generate models that combine substrate-based and protein-based approaches. In silico approaches include homology modeling, quantitative structure-activity relationships, virtual ligand screening, similarity and pharmacophore searching, data mining, and data analysis tools. These strategies have been frequently used in the discovery and optimization of
Voltage-gated Na+ channels have positively charged transmembrane helices, the S4 segments, that move in response to changes of membrane voltage, driving conformational changes within each channel that open or close its activation gate. According to current views (1, 2), conformational changes in each of the four domains of a Na+ channel, or each subunit of a K+ channel, are followed by a concerted step, a single event, that opens the gate, allowing flux through the pore. The S4 movements associated with the early conformational changes have been detected with labeling experiments (3, 4), but the nature of the concerted step is unknown. In this paper and the following one, the possibility is explored that the concerted step for a Na+ channel consists of liberating a calcium ion bound in the channel lumen.. Calcium and other divalent cations have well-documented effects on the properties of Na+ channels (5). These effects were conveniently summarized by Frankenhaueser and Hodgkin (6), who said ...
1. ATP-sensitive potassium (KATP) channels are composed of pore-forming Kir6.2 and regulatory SUR subunits. A truncated isoform of Kir6.2, Kir6.2DeltaC26, forms ATP-sensitive channels in the absence of SUR1, suggesting the ATP-inhibitory site lies on Kir6.2. 2. Previous studies have shown that mutation of the lysine residue at position 185 (K185) in the C-terminus of Kir6.2 to glutamine, decreased the channel sensitivity to ATP without affecting the single-channel conductance or the intrinsic channel kinetics. This mutation also impaired 8-azido[32P]-ATP binding to Kir6.2. 3. To determine if K185 interacts directly with ATP, we made a range of mutations at this position, and examined the effect on the channel ATP sensitivity by recording macroscopic currents in membrane patches excised from Xenopus oocytes expressing wild-type or mutant Kir6.2DeltaC26. 4. Substitution of K185 by a positively charged amino acid (arginine) had no substantial effect on the sensitivity of the channel to ATP. Mutation to a
We built profiles based on hidden Markov models (HMMs) of each ion channel family (Fig. 1) (Yu and Catterall, 2004) using the sequences corresponding to the minimal pore structure (i.e., the pore loop and the flanking M1/S5 and M2/S6 transmembrane segments). We interrogated the nonredundant protein database, RefSeq of the National Center for Biotechnology Information, using each HMM profile (Yu et al., 2004). This search revealed 143 genes that encode related ion channel proteins. The amino acid sequence relationships of their minimal pore structures are illustrated in Fig. 1. We found 21 proteins related to four-domain NaV and CaV channels; two novel two-domain relatives of ion channel proteins (TPC); 90 proteins related to one-domain voltage-gated potassium channels, including 40 KV channels, eight calcium-activated potassium (KCa) channels, 10 CNG and HCN channels, and 32 TRP channels and relatives; and 30 proteins related to the Kir and K2P channels. We verified that these families are ...
The cognitive enhancer XE991 interacts with K(+) channels consisting of KCNQ2 and KCNQ3 heteromultimers to block the M-current. XE991 can also block KCNQ1 K(+) channels expressed in oocytes, but sensitivity is reduced when the channels are coexpressed with minK (KCNE1). The purpose of the study was to examine the interaction of XE991 with other types of K(+) channel, especially those in the basolateral membranes of murine epithelia. K(+) channel blockade was measured by the inhibition of chloride secretion resulting from depolarization. XE991 inhibited the chloride secretory current in colonic epithelia by an interaction with basolateral K(+) channels when forskolin was used as the stimulus. However, when 1-ethyl-2-benzimidazolinone (EBIO) was used to stimulate chloride secretion, XE991 was ineffective unless charybdotoxin was also present. Because EBIO also activates Ca(2+)-sensitive K(+) channels, whereas forskolin activates only cAMP-sensitive K(+) channels, it is concluded that the latter ...
Magnesium ions are the most abundant divalent intracellular cations and are essential for life, as they play key roles in signaling, nucleic acid action and metabolism. Mg2+-deficiency is associated with diseases affecting the heart, muscle, bone, immune and nervous system, so it is very important to fully understand this ion uptake system. The ~200 kDa pentameric membrane channel CorA is the major Mg2+ uptake system in bacteria and a homolog of the eukaryotic mitochondrial Mrs2 proteins which it can complement. CorA contributes to Mg2+ homeostasis through a negative feedback loop, where Mg2+ binding at the subunit interface leads to channel closure and low Mg2+ concentrations stabilize the open conformation. Electron paramagnetic resonance (EPR) spectroscopic studies of purified CorA revealed large quaternary conformational changes associated with magnesium binding/unbinding. Using single-particle cryo-EM, we have determined the structure for the closed magnesium-bound state of CorA at a ...
Definition of Voltage-gated channel in the Financial Dictionary - by Free online English dictionary and encyclopedia. What is Voltage-gated channel? Meaning of Voltage-gated channel as a finance term. What does Voltage-gated channel mean in finance?
TRPC1 is an ion channel located on the plasma membrane of numerous human and animal cell types. [3] It is a nonspecific cation channel, which means that both sodium and calcium ions can pass through it. TRPC1 is thought to mediate calcium entry in response to depletion of endoplasmic calcium stores or activation of receptors coupled to the phospholipase C system. In HEK293 cells the unitary current-voltage relationship of endogenous TRPC1 channels is almost linear, with a slope conductance of about 17 pS. The extrapolated reversal potential of TRPC1 channels is +30 mV.[4] The TRPC1 protein is widely expressed throughout the mammalian brain and has a similar corticolimbic expression pattern as TRPC4 and TRPC5. [5][6] The highest density of TRPC1 protein is found in the lateral septum, an area with dense TRPC4 expression, and hippocampus and prefrontal cortex, areas with dense TRPC5 expression.[6] ...