• Figure 2: Pseudosymmetric architecture of ion channels formed from 2, 3, 4, or 5 protein subunits or multiple repeated domains in a single subunit. (scholarpedia.org)
  • 10. Scott VE, Rettig J, Parcej DN, Keen JN, Findlay JB, Pongs O, and Dolly JO (1994) Primary structure of a β subunit of α-dendrotoxin-sensitive K + channels from bovine brain. (aspetjournals.org)
  • 11. Rettig J, Heinemann SH, Wunder F, Lorra C, Parcej DN, Dolly JO, and Pongs O (1994) Inactivation properties of voltage-gated K + channels altered by presence of β-subunit. (aspetjournals.org)
  • 13. Rhodes KJ, Keilbaugh SA, Barrezueta NX, Lopez KL, and Trimmer JS (1995) Association and colocalization of K + channel α-and β-subunit polypeptides in rat brain. (aspetjournals.org)
  • Here, removal of intact α 6 protein from cerebellar granule cells allowed perturbations in other subunit levels to be studied. (jneurosci.org)
  • The structures of AMPA receptors in complex with auxiliary proteins are resolved by cryo-electron microscopy, and reveal conformational and permeation pathway changes that are associated with activation and desensitization of ionotropic glutamate receptors. (nature.com)
  • Neurons in the OLFACTORY EPITHELIUM with proteins ( RECEPTORS, ODORANT ) that bind, and thus detect, odorants. (lookformedical.com)
  • Though researchers' attention and this Viewpoint focus on a few famous ion channels that are considered the usual suspects as MS mechanosensors, we also discuss some of the more unusual suspects, such as G-protein coupled receptors. (stanford.edu)
  • Molecular biology has shown that the nicotinic and muscarinic receptors belong to distinct protein superfamilies . (wikidoc.org)
  • In contrast, the mAChRs are not ion channels, but belong instead to the superfamily of G-protein-coupled receptors that activate other ionic channels via a second messenger cascade. (wikidoc.org)
  • K + channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. (embl.de)
  • Marine toxins have potent actions on diverse sodium ion channels regulated by transmembrane voltage (voltage-gated ion channels) or by neurotransmitters (nicotinic acetylcholine receptor channels). (mdpi.com)
  • This review examines the historical perspective of the study of conotoxin peptides active on sodium channels gated by transmembrane voltage, which has led to recent advances in ion channel research made possible with the exploitation of the diversity of these marine toxins. (mdpi.com)
  • Inwardly rectifying potassium (Kir) channels open at the 'helix bundle crossing' (HBC), formed by the M2 helices at the cytoplasmic end of the transmembrane pore. (nature.com)
  • Kir channels consist of only two transmembrane helices plus an extensive C-terminal cytoplasmic tail of the channel pore. (nature.com)
  • Thus, when open, potassium ion-selective channels and anion channels hyperpolarize cells (cause the membrane potential to become more negative), whereas sodium- or calcium-selective channels and non-selective cation channels depolarize cells (cause the membrane potential to become more positive). (scholarpedia.org)
  • K2P potassium channels regulate excitability by affecting cellular resting membrane potential in the brain, cardiovascular system, immune cells, and sensory organs. (bvsalud.org)
  • Potassium channels are present in all types of cells and play critical roles in control of multiple physiological processes. (nature.com)
  • 3. Stuhmer W, Ruppersberg JP, Schroter KH, Sakmann B, Stocker M, Giese KP, Perschke A, Baumann A, and Pongs O (1989) Molecular basis of functional diversity of voltage-gated potassium channels in mammalian brain. (aspetjournals.org)
  • 4. Yokoyama S, Imoto K, Kawamura T, Higashida H, Iwabe N, Miyata T, and Numa S (1989) Potassium channels from NG108-15 neuroblastoma-glioma hybrid cells: primary structure and functional expression from cDNAs. (aspetjournals.org)
  • These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. (embl.de)
  • Molecular dynamics simulations show how protonation of Kir2.2[G178D], or the D173 pore-lining residues, changes solvation, K + ion occupancy, and K + conductance. (nature.com)
  • Ion channel gating and conductance are classically understood as separate processes. (nature.com)
  • The present data reveal how individual protonation events change the electrostatic microenvironment of the pore, resulting in step-wise alterations of ion pooling, and hence conductance, that appear as 'gated' substates. (nature.com)
  • In the G178D structure, the HBC gate is slightly wider than in previous structures, and molecular dynamics (MD) simulations demonstrate rapid wetting of the G178D pore at the HBC region, followed by further expansion and K + conductance through the channel. (nature.com)
  • Cytoplasmic calcium signals are generated by the opening of Ca 2+ -permeable ion channels that let Ca 2+ ions flow into the cytoplasm. (scholarpedia.org)
  • Central to this surveillance system is the movement of calcium ions into and out of cells. (elifesciences.org)
  • Calcium ions are normally kept at very low levels inside of cells and subtle changes in these levels relay information about the external environment. (elifesciences.org)
  • In the case of plant roots, changes in the concentration of calcium ions herald essential information about soil conditions and the presence of microorganisms, and in turn trigger appropriate responses. (elifesciences.org)
  • Calcium ion signals are essential for peas, beans and other members of the legume family to form close relationships (known as symbioses) with soil bacteria called rhizobia. (elifesciences.org)
  • Further experiments found that the channel formed by the mutated CNGC protein is leaky and allows calcium ions to enter the cell in the absence of any cue from the environment. (elifesciences.org)
  • The leaky entry of calcium ions likely confuses the plant's surveillance system, which disturbs the normal development of the root. (elifesciences.org)
  • For this purpose, WIN 55,212-2 was injected in pregnant wistar rats from gestation day 5 to 20 and a detailed analysis of the levels of the neurotrophin brain-derived neurotrophic factor (BDNF) as well as of the signaling molecules extracellular signal-regulated kinase (ERK)1/2 and alpha-calcium/calmodulin-dependent protein kinase II (alpha-CaMKII) was carried out in adult offspring. (researchgate.net)
  • As a core metal ion in signaling transduction, calcium content is maintained in dynamic balance under normal circumstances. (mdpi.com)
  • This channel is activated by signalling molecules inside cells, called 'cyclic nucleotides', and its activity ultimately leads to calcium ions flowing into the sperm cell's tail. (elifesciences.org)
  • This influx of calcium ions in turn controls the beating of the tail and, thereby, steers the sperm cell towards the egg. (elifesciences.org)
  • In zebrafish sperm, a more alkaline pH inside the cell causes calcium ions to flow in and this influx of calcium ions triggers a unique spinning-like swimming movement that is different from the swimming of other sperm from other species. (elifesciences.org)
  • The results reveal a mechanism by which quantitative competition between channel subunits for tetramer assembly can impact the phenotype of the mutation carrier. (elifesciences.org)
  • While most functions are attributed to protein kinase A, accumulating evidence suggests that not all nuclear cyclic AMP-dependent effects are mediated by this kinase, implying that other effectors may be involved. (bvsalud.org)
  • Here we explore the nuclear roles of Exchange Protein Activated by cyclic AMP 1. (bvsalud.org)
  • This phenomenon depends on intrinsically disordered regions present at its amino-terminus and is independent of protein kinase A. Finally, we demonstrate that nuclear Exchange Protein Activated by cyclic AMP 1 condensates assemble at genomic loci on chromosome 6 in the proximity of Histone Locus Bodies and promote the transcription of a histone gene cluster. (bvsalud.org)
  • Cyclic nucleotide-gated channel (CNGC) family members mediate Ca 2+ influx from cellular stores in plants (Charpentier et al. (elifesciences.org)
  • In sea urchin sperm, a cyclic nucleotide-gated K + channel (CNGK) mediates a cGMP-induced hyperpolarization that evokes Ca 2+ influx. (elifesciences.org)
  • The ability of ion channels to accomplish these three physiological functions also requires the housekeeping operation of another class of membrane proteins, the transporters and pumps, to set up standing ion concentration gradients across cell membranes. (scholarpedia.org)
  • Proton-coupled oligopeptide transporters belong to the major facilitator superfamily (MFS) of membrane transporters. (philipwfowler.me)
  • Our results identify several salt bridges that stabilize outward-facing conformations and we show that, for all the current structures of MFS transporters, the first two helices of each of the four inverted-topology repeat units form half of either the periplasmic or cytoplasmic gate and that these function cooperatively in a scissor-like motion to control access to the peptide binding site during transport. (philipwfowler.me)
  • The diffusion of Na + and K + across the receptor causes depolarization, the end-plate potential, that opens voltage-gated sodium channels , which allows for firing of the action potential and potentially muscular contraction. (wikidoc.org)
  • The majority of channels have three, four, or five homologous or identical subunits, arranged in circular symmetry, forming a single aqueous pore at the axial intersection ( Figure 2 ). (scholarpedia.org)
  • [1] The cytoplasm side of the nAChR receptor has rings of high negative charge that determine the specific cation specificity of the receptor and remove the hydration shell often formed by ions in aqueous solution. (wikidoc.org)
  • However, one set of channels (ClC chloride channels) has two homologous subunits forming one pore in each of the subunits. (scholarpedia.org)
  • Perhaps there are 500 genes for pore-forming and accessory subunits of channels. (scholarpedia.org)
  • In addition many of these channels have smaller accessory subunits that typically do not contribute to the actual pore. (scholarpedia.org)
  • All K + channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). (embl.de)
  • Introduced negative charges at the HBC (G178D) in Kir2.2 channels forces opening, allowing pore wetting and free movement of permeant ions between the cytoplasm and the inner cavity. (nature.com)
  • In the intermediate region of the receptor, within the pore lumen, valine and leucine residues (Val 255 and Leu 251) define a hydrophobic region which the dehydrated ion must pass through. (wikidoc.org)
  • The nAChRs are ligand -gated ion channels , and, like other members of the " cys-loop " ligand-gated ion channel superfamily, are composed of five protein subunits symmetrically arranged like staves around a barrel. (wikidoc.org)
  • Moreover, our experiments identified TRPV4 channels as hitherto unappreciated contributors to neuronal Na + loading on metabolic failure, suggesting this pathway as a possible target to ameliorate excitotoxic damage. (jneurosci.org)
  • They evolve and increase in number through phylogeny and can be placed in gene families and superfamilies according to their sequence similarities. (scholarpedia.org)
  • 1. McKinnon D (1989) Isolation of a cDNA clone coding for a putative second potassium channel indicates the existence of a gene family. (aspetjournals.org)
  • 9. Grissmer S, Dethlefs B, Wasmuth JJ, Goldin AL, Gutman GA, Cahalan MD, and Chandy KG (1990) Expression and chromosomal localization of a lymphocyte K + channel gene. (aspetjournals.org)
  • They were initially cloned as a result of a search for proteins involved in cardiac arhythmia. (embl.de)
  • 8. Paulmichl M, Nasmith P, Hellmiss R, Reed K, Boyle WA, Nerbonne JM, Peralta EG, and Clapham DE (1991) Cloning and expression of a rat cardiac delayed rectifier potassium channel. (aspetjournals.org)
  • The syndrome is caused by changes in the structure and function of certain cardiac ion channels and reduced expression of Connexin 43 (Cx43) in the Right Ventricle (RV), predominantly in the Right Ventricular Outflow Tract (VSVD), causing electromechanical abnormalities. (bvsalud.org)
  • In this study we have analyzed the gating kinetics of different mutations within key parts of this gating network. (philipwfowler.me)
  • Furthermore, the G-loop, which occurs at the centre of this extensive gating network, appears to become unstructured in the TS because mutations within this region have a 'catalytic' effect upon the channel gating kinetics. (philipwfowler.me)
  • We reported the crystal structure of a chicken Kir2.2[G178D] mutant channel 12 , in which the introduced G178D mutations at the HBC functionally stabilize the open conformation, a strategy used previously to obtain an open crystal structure of a bacterial homolog KirBac3.1 13 . (nature.com)
  • In a previous study we identified an extensive gating network within the inwardly rectifying Kir1.1 (ROMK) channel by combining systematic scanning mutagenesis and functional analysis with structural models of the channel in the closed, pre-open and open states. (philipwfowler.me)
  • KCNQ channels (also known as KQT-like channels) differ from other voltage-gated 6 TM helix channels, chiefly in that they possess no tetramerisation domain. (embl.de)
  • These findings provide important insights into the function of CNGCs and reveal how a small change in a channel protein can have far reaching effects on an organism. (elifesciences.org)
  • Single-channel recordings reveal striking, pH-dependent, subconductance behaviors in G178D (or G178E and equivalent Kir2.1[G177E]) mutant channels, with well-resolved non-cooperative subconductance levels. (nature.com)
  • In the present study, we carry out detailed single-channel analyses of cKir2.2[G178D] and hKir2.1[G177E] channels that reveal striking sub-state gating behavior. (nature.com)
  • Proteins, usually projecting from the cilia of olfactory receptor neurons , that specifically bind odorant molecules and trigger responses in the neurons . (lookformedical.com)
  • Fluorescence imaging is an indispensable method for analysis of diverse cellular and molecular processes, enabling, for example, detection of ions, second messengers, or metabolites. (jneurosci.org)
  • MS membrane proteins are essential for tissue development, cellular motion, osmotic homeostasis, and sensing external and self-generated mechanical cues like those responsible for touch and proprioception. (stanford.edu)
  • Ion concentration gradients and electrical forces drive the flow of ions through channel pores. (scholarpedia.org)
  • 2. Kamb A, Weir M, Rudy B, Varmus H, and Kenyon C (1989) Identification of genes from pattern formation, tyrosine kinase, and potassium channel families by DNA amplification. (aspetjournals.org)
  • Single-particle electron cryo-microscopy analysis of the mechanotransduction channel NOMPC reveals that it contains a bundle of four helical spring-shaped ankyrin repeat domains that undergo motion, potentially allowing mechanical movement of the cytoskeleton to be coupled to the opening of the channel. (nature.com)
  • Mechanosensitive membrane proteins: Usual and unusual suspects in mediating mechanotransduction. (stanford.edu)
  • During protein synthesis within the ribosome, transfer RNAs (tRNAs) move sequentially through different sites as their attached amino acids are transferred onto the growing protein chain. (nature.com)
  • An acetylcholine receptor (abbreviated AChR ) is an integral membrane protein that responds to the binding of the neurotransmitter acetylcholine . (wikidoc.org)
  • The muscarine cholinergic receptor activates a G protein when bound to ex.c. ach. (wikidoc.org)
  • Here, we describe a chemogenetic strategy termed CATKLAMP (Covalent Activation of TREK family K+ channels to cLAmp Membrane Potential) that leverages the discovery of a site in the K2P modulator pocket that reacts with electrophile-bearing derivatives of a TREK subfamily small molecule activator, ML335, to activate the channel irreversibly. (bvsalud.org)
  • the overall structure of this ion channel is found to share some common features with voltage-gated ion channels, although several unique, TRP-specific features are also characterized. (nature.com)
  • Studies of these toxins have focused on varied aspects of venom peptides ranging from evolutionary relationships of predator and prey, biological actions on excitable tissues, potential application as pharmacological intervention in disease therapy, and as part of multiple experimental approaches towards an understanding of the atomistic characterization of ion channel structure. (mdpi.com)
  • These results suggest that the structure of the transition state (TS), which connects the pre-open and closed states of the channel, more closely resembles the structure of the pre-open state. (philipwfowler.me)
  • This implicates expansion of the HBC as a critical step in Kir channel opening, as seen in a recent Kir6.2 structure 11 . (nature.com)
  • They fall into a few large families of closely related proteins and many small outlying families that lack any known evolutionary relationship to the others. (scholarpedia.org)
  • Together, our findings exemplify a new means to alter K2P channel activity that should facilitate studies both molecular and systems level studies of K2P function and enable the search for new K2P modulators. (bvsalud.org)
  • This entry represents a region found at the C terminus of these proteins. (embl.de)
  • It was previously thought that this CNGK channel is found only in animals without a backbone (i.e. in invertebrates). (elifesciences.org)
  • These findings suggest that while channel proteins found in sperm cells from different species look similar and serve similar roles, they are activated in ways that can be very different. (elifesciences.org)
  • A picture is emerging of sperm channel orthologues that employ different activation mechanisms and serve different functions. (elifesciences.org)
  • brush resides in a cluster of redundant CNGCs encoding subunits which resemble metazoan voltage-gated potassium (Kv1-Kv4) channels in assembly and gating properties. (elifesciences.org)
  • Flux of ions through ion channels contributes to the electrolyte movements required for volume regulation of single cells and for the net polarized transport of salt across epithelia like gut, kidney, or the choroid plexus. (scholarpedia.org)
  • Single-particle cryo-electron microscopy has enabled the structures of large proteins to be elucidated. (nature.com)
  • 2007). Here, we report the unusual genetic behavior of a quantitative gain-of-function CNGC mutation ( brush ) in Lotus japonicus resulting in a leaky tetrameric channel. (elifesciences.org)
  • This Viewpoint, which accompanies a Special Issue focusing on membrane mechanosensors, discusses unifying and unique features of both established and emerging mechanosensitive (MS) membrane proteins, their distribution across protein families and phyla, and current and future challenges in the study of these important proteins and their partners. (stanford.edu)
  • Ion channels set up the resting membrane potentials of all cells. (scholarpedia.org)
  • Since the flow of ions moves charge and constitutes an electric current, channel opening and closing underlie all electrical signaling of electrically excitable cells such as nerve and muscle. (scholarpedia.org)
  • In 2009, researchers identified a potassium ion channel, called CNGK, that starts the electrical signal in the sperm cells of sea urchins. (elifesciences.org)
  • including some of the researchers involved in the 2009 work - now report that the CNGK channel also exists in the sperm cells of a freshwater fish, the zebrafish. (elifesciences.org)
  • Unexpectedly, the CNGK channel is located in the heads of this fish's sperm cells rather than in the tails. (elifesciences.org)
  • 5. Chandy KG, Williams CB, Spencer RH, Aguilar BA, Ghanshani S, Tempel BL, and Gutman GA (1990) A family of three mouse potassium channel genes with intronless coding regions. (aspetjournals.org)
  • The 2TM domain family comprises inward-rectifying K + channels. (embl.de)
  • 12. Kim E, Niethammer M, Rothschild A, Jan YN, and Sheng M (1995) Clustering of Shaker-type K + channels by interaction with a family of membrane-associated guanylate kinases. (aspetjournals.org)