Several small conductance calcium activated potassium channels. Medical search. Frequent questions

SK channels are a type of ion channel allowing potassium cations to cross the cell membrane and are activated (opened) by an increase in the concentration of intracellular calcium through N-type calcium channels. (wikipedia.org)
The SK channel gating mechanism is controlled by intracellular calcium levels. (wikipedia.org)
The protein encoded by this gene is part of a potentially heterotetrameric voltage-independent potassium channel that is activated by intracellular calcium. (thermofisher.com)
Potassium channels whose activation is dependent on intracellular calcium concentrations. (harvard.edu)
It was soon shown that this effect depended on an increase in intracellular calcium (Cai2+) ( Whittam, 1968 ), and that the calcium sensor was located at the inside of the membrane ( Blum and Hoffman, 1972 ). (conicyt.cl)

SK channels (small conductance calcium-activated potassium channels) are a subfamily of calcium-activated potassium channels. (wikipedia.org)
This gene is similar to other KCNN family potassium channel genes, but it differs enough to possibly be considered as part of a new subfamily. (thermofisher.com)

The small conductance (SK) channels inhibitor, apamin, that selectively blocks I(A)(HP), reduced the AHP in neurons from trained, naïve, and pseudotrained rats to a similar extent, thus maintaining the difference in AHP amplitude between neurons from trained rats and controls. (nih.gov)
The hyperpolarization response was decreased to a similar extent by either inhibition of SK3 channel with the selective SK antagonist, apamin, or by inhibition of the BK channel with the selective antagonist, iberiotoxin (IbTX). (elsevierpure.com)
Apamin-sensitive calcium-activated potassium currents in rabbit ventricles with chronic myocardial infarction. (harvard.edu)
Based on differences in unitary conductances, sensitivity to drugs, and voltage-dependence, this allowed the classification of the channels as small (SK), with unitary conductances of 4 - 14 pS that are blocked by apamin and are insensitive to voltage. (conicyt.cl)
The blocker of ATP-modulated potassium channels (K(ATP)), glibenclamide (10 microM), and of small conductance calcium-activated potassium channels (SK(Ca)), apamin (30 nM), each failed to affect ODQ-sensitive or -resistant relaxations to DEA NONOate (n=3). (ox.ac.uk)
Apamin, a selective blocker of the SK channels responsible for part of the slow afterhyperpolarisation reduced, but did not abolish, the amplitude of the post-burst afterhyperpolarisation. (ox.ac.uk)
Notably the L-type Ca(2+) channel antagonist, nifedipine, was more effective than apamin at reducing the post-burst afterhyperpolarisation. (ox.ac.uk)
We suggest that Ca(2+) entry through L-type channels during an epileptiform event is selectively coupled to both apamin-sensitive and -insensitive Ca(2+) activated K(+) channels. (ox.ac.uk)
To enhance the genetic findings, we examined the flexibility of apamin, a KCa2 channel allosteric inhibi. (adenosine-kinase.com)

Small (SK) and intermediate (IK) conductance calcium-activated potassium channels are candidate ion channels for the regulation of excitability in nociceptive neurones. (dundee.ac.uk)
SK4 is often referred to as IK (Intermediate conductance) due to its higher conductance 20 - 80 pS. (wikipedia.org)
Intermediate (IK) channels, on the other hand, have conductances of 11- 40 pS, are voltage-independent, may be blocked by iberiotoxin and charybdotoxin (Ch Tx), and are found in red and white blood cells, colon, lung, pancreas, and other tissues. (conicyt.cl)
Brown BM, Shim H, Christophersen P, Wulff H. Pharmacology of Small- and Intermediate-Conductance Calcium-Activated Potassium Channels. (ucdavis.edu)
The objective of this study was to investigate the contribution of small or intermediate conductance calcium-activated potassium channels (SKca & IKca) in modulating vascular function of MA in this model. (pacific.edu)
The remaining EDV to ACh which is referred to as the L-NAME/Indo-insensitive component, or EDHF-type relaxation was subsequently blocked by inhibiting intermediate (but not small) conductance calcium-activated potassium channels in MA of diabetic model. (pacific.edu)
Tom's graduate studies were sponsored by a Biotechnology and Biological Sciences Research Council (BBSRC) Collaborative Award in Science and Engineering (CASE) fellowship, with Boehringer Ingelheim as an industrial sponsor, and focused on the role of the astrocytic intermediate-conductance calcium-activated potassium channel in neurovascular coupling. (umaryland.edu)

This was better defined when recordings were made of single channels in many different preparations in combination with the use of selective blockers. (conicyt.cl)
The contribution from cGMP-dependent signalling pathways was examined by exposing arteries to 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), a selective inhibitor of soluble guanylyl cyclase, while the contribution through potassium channels was assessed with different sub-type-selective potassium channel blockers. (ox.ac.uk)

Dequalinium Chloride (DECA) is a PKC inhibitor and high-affinity blocker CNGA1 channel, and nearly as effective on heteromeric CNGA1+CNGB1 channels. (ncats.io)
1 mM), an inhibitor of voltage-gated potassium channels (Kv), failed to modify DEA NONOate-evoked relaxation. (ox.ac.uk)

Early electrical activity and calcium influx regulate crucial aspects of neuronal development. (units.it)
In this study, we examined which potassium current is reduced by learning and how the effect of noradrenalin (NE) on neuronal excitability is modified by such reduction. (nih.gov)

Her laboratory is particularly interested in the voltage-gated Kv1.3 and the calcium-activated KCa3.1 channels in immune cells and in the calcium-activated KCa2/3 channels in the cardiovascular and nervous system. (ucdavis.edu)
Small-conductance calcium-activated potassium (KCa2) channels happen to be implicated in synaptic plasticity, cognition, and addiction, and modulating these channels can enrich the extinction understanding of food-seeking and dread behaviors. (adenosine-kinase.com)
On the other hand, the particular genes that regulate extinction mastering have not been identified, and it truly is presently mysterious if modulating KCa2 channels can facilitate extinction of alcoholassociated recollections. (adenosine-kinase.com)
So, the objective of this review was to find out should the genes that encode KCa2 channels (Kcnn1-3)ACNP 53rd Once-a-year MeetingAbstractsSpredict extinction studying in BXD recombinant inbred (RI) strains of mice and when blocking KCa2 channels enhances extinction learning of alcoholic beverages cues. (adenosine-kinase.com)

This is accomplished through the hyperpolarizing leak of positively charged potassium ions along their concentration gradient into the extracellular space. (wikipedia.org)
The concentration gradients are maintained by the sodium/potassium ATP pump (in an energy-dependent process) that transports sodium ions out of the cell and potassium ions into the cell. (medscape.com)
This active transport creates a concentration gradient that favors the extracellular diffusion of potassium ions. (medscape.com)
In addition, because the nerve membrane is permeable to potassium ions and impermeable to sodium ions, 95% of the ionic leak in excitable cells is caused by K+ ions in the form of an outward flux, accounting for the negative resting potential. (medscape.com)
Once membrane depolarization is complete, the membrane becomes impermeable to sodium ions again, and the conductance of potassium ions into the cell increases. (medscape.com)

In addition, using Western blotting, we sought to determine the level of protein expression of SK and IK channels in sensory nervous tissues following induction of inflammation (Freund's Complete Adjuvant (FCA) arthritis model) or nerve injury (chronic constriction injury model). (dundee.ac.uk)
In addition, SK potassium channels are tightly associated with the protein calmodulin, which accounts for the calcium sensitivity of these channels. (wikipedia.org)
Even in the absence of calcium, the SK channel binds to the C-lobe of the protein calmodulin (CaM). (wikipedia.org)
In addition, the protein expression level of the SK1, SK2, and SK3 channels was also similar in all groups. (nih.gov)
The encoded protein may be part of the predominant calcium-activated potassium channel in T-lymphocytes. (thermofisher.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)
On the other hand, BK channels have an aspartate-rich Ca-sensing region (a «calcium bowl») in the channel protein itself, which confers most of the Ca-sensitivity to the channel, although a second Ca-sensor also seems to be present ( Schreiber and Salkoff, 1997 ). (conicyt.cl)
Here, his work (sponsored by two American Heart Association Founder's Affiliate Postdoctoral Fellowships) focused on the role of vascular ion channels and G-protein coupled receptors in the control of brain blood flow. (umaryland.edu)

Such AHP reduction is caused by decreased conductance of one or more of the calcium-dependent potassium currents, I(AHP) and sI(AHP), that mediate the medium and slow AHPs. (nih.gov)
Figure 1: Ca V 1.3 and BK channels mediate the major cation currents in electrosensory cells. (nature.com)
Cerebellar ataxia by enhanced Ca(V)2.1 currents is alleviated by Ca2+-dependent K+-channel activators in Cacna1a(S218L) mutant mice. (harvard.edu)
These conclusions were, however, apparently contradicted by elegant experiments done on internally-perfused snail neurons, in which neither the injection of calmodulin, nor of the calmodulin-antagonist, trifluoperazine, were able to modify Ca-activated K currents ( Levitan and Levitan, 1986 ). (conicyt.cl)
This increased intrinsic excitability of DCN neurons is accompanied by a reduction in after-hyperpolarization currents mediated by small-conductance calcium-activated potassium (SK) channels. (foundationdystoniaresearch.org)
The recently identified 2-pore domain potassium (K2P) channels are believed to be responsible for leak K+ currents. (medscape.com)

Thiazides cause vasodilation by activating calcium-activated potassium channels (large conductance) in vascular smooth muscles and inhibiting various carbonic anhydrases in vascular tissue. (drugbank.com)
Endothelium-dependent hyperpolarizing factors (EDHF) is an important regulator of vascular tone, especially in small vessels such as MA. (pacific.edu)
The relative functional importance of potassium channels and cGMP-dependent pathways in the relaxation of vascular smooth muscle to the novel nitric oxide donor, diethylamine NONOate (DEA NONOate), was investigated in a resistance artery. (ox.ac.uk)
Longden T , Nelson M (2015) " Vascular Inward Rectifier K+ Channels as External K+ Sensors in the Control of Cerebral Blood Flow " Microcirculation , 22(3): 183-196. (umaryland.edu)

Analysis of Single Nucleotide Polymorphisms (SNPs) of the small-conductance calcium activated potassium channel (SK3) gene as genetic modifier of the cardiac phenotype in myotonic dystrophy type 1 patients. (cdc.gov)
Finally, it seems appropriate to consider the "sodium channel syndrome" (mutations in the gene of the α subunit of the sodium channel, SCN5A gene) as a single clinical entity that may manifest in a wide range of phenotypes, to thus have a better insight on these cardiac syndromes and potential outcomes for their clinical treatment. (bvsalud.org)

Dr. Wulff is considered an expert on potassium channel pharmacology and the work in her laboratory focuses on the design of new potassium channel modulators as research tools and as potential drugs. (ucdavis.edu)

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)
This results in an increase in potassium excretion via the sodium-potassium exchange mechanism. (drugbank.com)
The antihypertensive mechanism of cyclothiazide is less well understood although it may be mediated through its action on carbonic anhydrases in the smooth muscle or through its action on the large-conductance calcium-activated potassium (KCa) channel, also found in the smooth muscle. (drugbank.com)

Calcium enters the cell via voltage activated calcium channels as well as through NMDA receptors. (wikipedia.org)

Small-conductance calcium- activated potassium (SK) channels regulate action potential firing and shape calcium influx through feedback regulation in mature neurons. (units.it)
To allow studies on the contribution of SK channels to different phases of development of single neurons and networks, we have performed a detailed in situ hybridization mapping study, providing comprehensive distribution profiles of all three SK subunits (SK1, SK2, and SK3) in the rat CNS during embryonic and postnatal development. (units.it)
Additionally, this study shows how the postnatal ontogenetic patterns lead to the adult expression map for each SK channel subunit and how their coexpression in the same regions or neurons varies throughout development. (units.it)
SK channels control action potential discharge frequency in hippocampal neurons, midbrain dopaminergic neurons, dorsal vagal neurons, sympathetic neurons, nucleus reticularis thalamic neurons, inferior olive neurons, spinal and hypoglossal motoneurons, mitral cells in the olfactory bulb, and cortical neurons. (wikipedia.org)
Effects of calcium-activated potassium channel modulators on afterhyperpolarizing potentials in identified motor and mechanosensory neurons of the medicinal leech. (harvard.edu)
On the other hand, these recent studies apparently also support the lack of involvement of calmodulin in the gating of the BK channels studied in Helix neurons by Levitan and Levitan (1986) . (conicyt.cl)

SK channel activation can mediate neuroprotection in various models of cell death. (wikipedia.org)
Here we show that the voltage-gated calcium channel Ca V 1.3 and the big conductance calcium-activated potassium (BK) channel are preferentially expressed by electrosensory cells in little skate ( Leucoraja erinacea ) and functionally couple to mediate electrosensory cell membrane voltage oscillations, which are important for the detection of specific, weak electrical signals. (nature.com)
Both channels exhibit unique properties compared with their mammalian orthologues that support electrosensory functions: structural adaptations in Ca V 1.3 mediate a low-voltage threshold for activation, and alterations in BK support specifically tuned voltage oscillations. (nature.com)
The nAChR is coupled to the activation of small-conductance calcium-activated SK2 potassium channels expressed in the IHCs, which mediate the hyperpolarization of IHC membrane potential in response to MOC efferent activation ( Glowatzki and Fuchs, 2000 ). (frontiersin.org)
Taken together, our results suggest that multiphasic On/Off responses may mediate olfactory navigation and that SK channels may account for these responses. (hal.science)
These SK channels are abundant in the nervous system, where they mediate slow after-hyperpolarizations that modulate excitability. (conicyt.cl)

TWIK-related acid-sensitive potassium channel 1 (TASK-1 encoded by KCNK3) belongs to the family of two-pore domain potassium channels. (ersjournals.com)

influx via the Gardos channel (IK(Ca)) in human erythrocytes. (lu.se)
Activation is followed by membrane hyperpolarization, which promotes calcium influx. (thermofisher.com)
Fluorescent assessment of cell membrane potential in native, split-opened CCD, demonstrated that selective activation of the Ca 2+ -permeable TRPV4 channel, thereby inducing Ca 2+ influx and elevating intracellular Ca2+ levels, activated both the SK3 channel and the BK channel leading to hyperpolarization of the cell membrane. (elsevierpure.com)
It is concluded that SK3 is functionally expressed in the distal nephron and collecting ducts where induction of TRPV4-mediated Ca 2+ influx, leading to elevated intracellular Ca 2+ levels, activates this high Ca 2+ - affinity K + channel. (elsevierpure.com)
Increases in excitability could also be achieved by strongly buffering intracellular Ca(2+) or by minimising Ca(2+) influx into the cell, specifically through L-type (but not N-type) voltage operated Ca(2+) channels. (ox.ac.uk)

Addition of both inhibitors produced a further depolarization, indicating cooperative effects of the two channels on Vm. (elsevierpure.com)
Later experiments, in which six different calmodulin-inhibitory drugs were tested on the Ca-activated K conductance of human RBCs, showed that all were potent inhibitors of this conductance and that their effect showed a correlation coefficient of 0.98 with that found on RBC Ca-ATPase, a membrane enzyme known to be activated by calmodulin ( Lackington and Orrego, 1981 ). (conicyt.cl)

The energy for this is provided by a sodium gradient established by sodium-potassium ATPases on the basolateral membrane. (drugbank.com)
Once sodium has entered the cell, it is transported out into the basolateral interstitium via the sodium-potassium ATPase, causing an increase in the osmolarity of the interstitium, thereby establishing an osmotic gradient for water reabsorption. (drugbank.com)

Our results are not consistent with the idea that EDHF is K + activating Na + /K + ATPase and K(IR) in this blood vessel. (lu.se)

Small-conductance, calcium-activated potassium channels from mammalian brain. (yale.edu)

K+ channel modulators for the treatment of neurological disorders and autoimmune diseases. (ucdavis.edu)

Hariharan A, Weir N, Robertson C, He L, Betsholtz C, Longden T (2020) " The ion channel and GPCR signaling toolkit of CNS pericytes " Frontiers in Cellular Neuroscience 14: 423. (umaryland.edu)

Wulff H, Castle NA, Pardo LA. Voltage-gated potassium channels as therapeutic targets. (ucdavis.edu)

Involvement of cyclic GMP and potassium channels in relaxation evoked by the nitric oxide donor, diethylamine NONOate, in the rat small isolated mesenteric artery. (ox.ac.uk)

Longden T , Hill-Eubanks D, Nelson M (2016) " Ion Channel Networks in the Control of Cerebral Blood Flow " Journal of Cerebral Blood Flow & Metabolism , 36(3): 492-512. (umaryland.edu)

The process restores the excess of intracellular potassium and extracellular sodium and reinstates the negative resting membrane potential. (medscape.com)

Discovery of Novel Activators of Large-Conductance Calcium-Activated Potassium Channels for the Treatment of Cerebellar Ataxia. (harvard.edu)

SK channels are thought to be involved in synaptic plasticity and therefore play important roles in learning and memory. (wikipedia.org)

A Hodgkin-Huxley-type neuron model with a small-conductance calcium-activated potassium (SK) channel reproduces physiological On/Off responses. (hal.science)
An activator of SK channels reduces DCN neuron firing frequency in acute cerebellar slices and improves the dystonic gait of Atcayji-hes mice. (foundationdystoniaresearch.org)

SK channels may assemble as homotetrameric channels or as heterotetrameric channels, consisting of more than one SK channel subtype. (wikipedia.org)
Hougaard et al (2009) Selective activation of the SK1 subtype of human small-conductance Ca2+-activated K+ channels by 4-(2-methyoxy-phenylcarbamoyloxymethyl)-piperidine-1-carboxylic acid tert-butyl ester (GW542573X) is dependent on serine 298 in Mol.Pharmacol. (tocris.com)

The time constant of SK channel activation is approximately 5 ms. When calcium levels are depleted, the time constant for channel deactivation ranges from 15-60 ms. All SK channels can be pharmacologically blocked by quaternary ammonium salts of a plant-derived neurotoxin bicuculline. (wikipedia.org)
The inhibitory action of ChTX suggests part of the cGMP-insensitive component involves the activation of potassium channels, a suggestion supported by the inhibitory actions of 4-AP and IbTX in the absence of cGMP. (ox.ac.uk)
Ca(2+) entry through L-type Ca(2+) channels helps terminate epileptiform activity by activation of a Ca(2+) dependent afterhyperpolarisation in hippocampal CA3. (ox.ac.uk)

These are usually highly regulated K + selective leak channels. (embl.de)

These functions, observed in the adult nervous system, make them ideal candidates to regulate activity- and calcium-dependent processes in neurodevelopment. (units.it)
However, to date little is known about the onset of expression and regions expressing SK channel subunits in the embryonic and postnatal development of the central nervous system (CNS). (units.it)
SK channels are expressed throughout the central nervous system. (wikipedia.org)

CAD-1883 is a selective positive allosteric modulator of SK channels (small-conductance, calcium-activated potassium ion channels). (neurologyadvisor.com)

Their early expression in embryonic development suggests an involvement of SK channels in the regulation of developmental processes. (units.it)
Functional states of the sodium channel (closed, open, and inactivated) and their structure help to understand the cardiac regulation processes. (bvsalud.org)

TASK-1 channels are sensitive to a wide array of physiological and pharmacological mediators that affect their activity such as unsaturated fatty acids, extracellular pH, hypoxia, anaesthetics and intracellular signalling pathways. (ersjournals.com)
Mutations in K + channel sequences can lead to a variety of clinical disorders exemplifying their physiological importance [ 3 ]. (ersjournals.com)
From a physiological and pathophysiological point of view, the conformational states of the sodium channel during heart function constitute a significant aspect for the diagnosis and treatment of heart diseases. (bvsalud.org)

CK2 serves to phosphorylate the SKCa-bound CaM at the T80 residue, rather than the channel helices themselves, to reduce calcium sensitivity. (wikipedia.org)

The three SK channel subunits display different developmental expression gradients in distinct CNS regions, with time points of expression and up- or downregulation that can be associated with a range of diverse developmental events. (units.it)
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)
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)
In addition, there are K + channel alpha-subunits that possess two P-domains. (embl.de)

SK potassium channels share the same basic architecture with Shaker-like voltage-gated potassium channels. (wikipedia.org)
These channels are considered to be voltage-independent, as they possess only two of seven positively charged amino acid residues that are typically seen in a prototypical voltage-gated potassium channel. (wikipedia.org)
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)

In CNT and CCD, main sites for K + secretion, the highest levels of expression were along the apical (luminal) cell membranes, including for both principal cells (PCs) and intercalated cells (ICs), posturing the channel for Ca 2+ - dependent K + secretion. (elsevierpure.com)
Case Report on: Very Early Afterdepolarizations in HiPSC-Cardiomyocytes-An Artifact by Big Conductance Calcium Activated Potassium Current (Ibk,Ca). Cells. (harvard.edu)
The presence in human red blood cells (RBCs) of a K permeability that was greatly enhanced by calcium was first reported by Gardós (1958) . (conicyt.cl)

Very recently, the sequencing of the genes that code for SK, IK and BK channels has allowed a definition of the mechanisms of channel gating and of the participation of calmodulin in it. (conicyt.cl)

A loop between the fifth and sixth transmembrane domains forms the potassium ion selectivity filter. (wikipedia.org)

The selectivity filter of all SK channel subtypes-whether SK1, SK2, SK3, or SK4-is highly conserved and reflects the selectivity seen in any potassium channel, a GYGD amino acid residue sequence on the pore-forming loop. (wikipedia.org)

Ca(2+)-activated K(+) channel-3.1 blocker TRAM-34 attenuates airway remodeling and eosinophilia in a murine asthma model. (harvard.edu)

This review summarises our current state of knowledge of the functional role of TASK-1 channels in the pulmonary circulation in health and disease, with special emphasis on current advancements in the field. (ersjournals.com)
Heart relaxation also stands out as an active process, dependent on the energetic output and on specific ion and enzymatic actions, with the role of sodium channel being outstanding in the functional process. (bvsalud.org)

Calmodulin participates as a subunit of the channel itself, bound to the cytoplasmic C-terminus region of the peptide called the calmodulin binding domain (CaMBD). (wikipedia.org)
When the N-lobe binds calcium, it traps the S4-S5 linker on the intracellular subunit of the SK channel. (wikipedia.org)

However, the contribution made to relaxation by potassium channels appears to be unmasked following pharmacological attenuation of cGMP-dependent signalling pathways. (ox.ac.uk)

Thus it is probably mediated by reduction in conductance of the other calcium-dependent potassium current, sI(AHP). (nih.gov)
The Ca 2+ -activated, maxi-K (BK) K + channel, with low Ca 2+ -binding affinity, is expressed in the distal tubule of the nephron and contributes to flow-dependent K+ secretion. (elsevierpure.com)
In conclusion, relaxation to DEA NONOate in the rat isolated, small mesenteric artery can occur via both cGMP-dependent (ODQ-sensitive) and -independent (ODQ-resistant) mechanisms. (ox.ac.uk)

A loop between S5 and S6-called the P-loop-provides the pore-forming region that always faces the center of the channel. (wikipedia.org)
This may only be accomplished when the channel pore is closed. (wikipedia.org)

Wulff H, Christophersen P, Colussi P, Chandy KG, Yarov-Yarovoy V. Antibodies and venom peptides: new modalities for ion channels. (ucdavis.edu)

We have used unique peptide-directed antisera to describe the immunocytochemical distribution of the known isoforms of these ion channels in dorsal root ganglia (DRG) and spinal cord of the rat. (dundee.ac.uk)

Recent studies show that modulation of TASK-1 channels, either directly or indirectly by targeting their regulatory mechanisms, has the potential to control pulmonary arterial tone in humans. (ersjournals.com)

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