Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Potassium Channels”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 505 records · Page 28Linked to original sources
PubMed1993

Potassium channel antagonists and vascular reactivity in stroke-prone spontaneously hypertensive rats.

The goal of this study was to characterize differences in contractile responsiveness to several potassium channel antagonists in vascular smooth muscle from stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto normotensive rats (WKY). Helically-cut strips of carotid arteries (endothelium removed) from SHRSP and WKY were mounted in muscle baths for measurement of isometric force generation. Contractile responses to tetraethylammonium (10(-4) to 3 x 10(-2) mol/L) and barium (3 x 10(-5) mol/L), blockers of the voltage-dependent and large conductance, calcium activated potassium channels, were greater in carotid arteries from SHRSP than in those from WKY. In contrast, contractile responses to the voltage-dependent potassium channel blockers 3,4-diamino-pyridine (10(-6) to 3 x 10(-3) mol/L) and sparteine (10(-6) to 3 x 10(-2) mol/L) in arteries from SHRSP did not differ from WKY values. Carotid arteries from SHRSP and WKY did not contract to apamin (10(-9) to 10(-6) mol/L), an antagonist of the small conductance, calcium activated potassium channel. Furthermore, relaxation responses to diazoxide (3 x 10(-4) mol/L), an activator of the ATP-sensitive potassium channel, and subsequent contractions to the ATP-sensitive potassium channel blocker glyburide (10(-8) to 3 x 10(-6) mol/L) in arteries from SHRSP did not differ from WKY values. Carotid artery segments from SHRSP were more sensitive to the contractile effects of elevated potassium than those from WKY. We conclude that altered activity of the large conductance, calcium activated potassium channel may play a role in the increased responsiveness observed in arteries from SHRSP.

4-Aminopyridine↗
PubMed1992

Calcium-activated potassium channels expressed from cloned complementary DNAs.

Calcium-activated potassium channels were expressed in Xenopus oocytes by injection of RNA transcribed in vitro from complementary DNAs derived from the slo locus of Drosophila melanogaster. Many cDNAs were found that encode closely related proteins of about 1200 aa. The predicted sequences of these proteins differ by the substitution of blocks of amino acids at five identified positions within the putative intracellular region between residues 327 and 797. Excised inside-out membrane patches showed potassium channel openings only with micromolar calcium present at the cytoplasmic side; activity increased steeply both with depolarization and with increasing calcium concentration. The single-channel conductance was 126 pS with symmetrical potassium concentrations. The mean open time of the channels was clearly different for channels having different substituent blocks of amino acids. The results suggest that alternative splicing gives rise to a large family of functionally diverse, calcium-activated potassium channels.

Amino Acid Sequence↗
PubMed1997

An ATP-sensitive potassium channel activator reduces infarct volume in focal cerebral ischemia in rats.

ATP-sensitive potassium channels are activated under hypoxic or ischemic conditions. The effects of ATP-sensitive potassium channel activators on cerebrovasculature and cerebral blood flow (CBF) are not well understood. We examined the effect of the ATP-sensitive potassium channel activator Y-26763 on focal cerebral ischemia in rats. In 24 spontaneously hypertensive rats, either Y-26763 (24 micrograms/kg) or vehicle was given by intracarotid infusion over 60 min, starting 30 min before photochemically induced thrombotic occlusion of the middle cerebral artery. CBF was measured by laser-Doppler flowmetry in the peri-ischemic penumbral cortex. Although Y-26763 lowered systemic blood pressure by 13 mmHg, the infarct volume assessed 3 days after the occlusion was significantly smaller in the Y-26763-treated group (n = 12, 71.2 +/- 22.0 mm3) than in the control group (n = 12, 94.7 +/- 20.4 mm3, P = 0.013). Y-26763 did not affect CBF before or after occlusion compared with CBF values of the control group. The results are consistent with the view that the activation of the ATP-sensitive potassium channel is neuroprotective in focal cerebral ischemia.

Adenosine Triphosphate↗
PubMed2002

Identification of domains that control the heteromeric assembly of Kir5.1/Kir4.0 potassium channels.

Heteromultimerization between different inwardly rectifying (Kir) potassium channel subunits is an important mechanism for the generation of functional diversity. However, little is known about the mechanisms that control this process and that prevent promiscuous interactions in cells that express many different Kir subunits. In this study, we have examined the heteromeric assembly of Kir5.1 with other Kir subunits and have shown that this subunit exhibits a highly selective interaction with members of the Kir4.0 subfamily and does not physically associate with other Kir subunits such as Kir1.1, Kir2.1, and Kir6.2. Furthermore, we have identified regions within the Kir4.1 subunit that appear to govern the specificity of this interaction. These results help us to understand the mechanisms that control Kir subunit recognition and assembly and how cells can express many different Kir channels while maintaining distinct subpopulations of homo- and heteromeric channels within the cell.

Amino Acid Sequence↗
PubMed1998

Influence of detergents on the function of cloned potassium channels.

The influence of detergents on cloned potassium channels expressed in Xenopus oocytes was investigated. Bath application of Triton X-100 caused a dose-dependent reduction of the peak current through the delayed rectifier channel rKv2.1 and a fast, time- and voltage-dependent, current inactivation. Onset of inactivation was observed at concentrations as low as 1 microM; at 100 microM inactivation proceeded with a time constant of about 50 ms at +50 mV. The effect of Triton did not compete with extracellular TEA and the tail current kinetics was accelerated, indicating that the molecular mechanism is not a simple open-channel block. In patch-clamp recordings the effects were readily reversible and application of detergents from the inside were most effective. Triton induced similar effects in hKv1.5 channels; for rKv1.1., d-eag, and Kir2.1 mainly a current reduction was observed. No effect of 100 microM Triton was found for the plant inward rectifier channel KAT1. Investigation of Shaker channel mutants revealed a dependence of the Triton effect upon the degree and nature of C-type inactivation. Only detergents with a long hydrophobic carbohydrate chain and a hydrophilic chain of the polyethyleneglycol type caused inactivation of rKv2.1 (e.g., Triton X-100, Thesit, Brij35 were active; CHAPS and MEGA-8 wre inactive). The presented data reveal that there are channel- and detergent-specific interactions which can result in fast inactivation leading to physiological effects similar to those exerted by local anesthetics and antiarrhythmic agents.

Animals↗
PubMed2003

MinK, MiRP1, and MiRP2 diversify Kv3.1 and Kv3.2 potassium channel gating.

High frequency firing in mammalian neurons requires ultra-rapid delayed rectifier potassium currents generated by homomeric or heteromeric assemblies of Kv3.1 and Kv3.2 potassium channel alpha subunits. Kv3.1 alpha subunits can also form slower activating channels by coassembling with MinK-related peptide 2 (MiRP2), a single transmembrane domain potassium channel ancillary subunit. Here, using channel subunits cloned from rat and expressed in Chinese hamster ovary cells, we show that modulation by MinK, MiRP1, and MiRP2 is a general mechanism for slowing of Kv3.1 and Kv3.2 channel activation and deactivation and acceleration of inactivation, creating a functionally diverse range of channel complexes. MiRP1 also negatively shifts the voltage dependence of Kv3.1 and Kv3.2 channel activation. Furthermore, MinK, MiRP1, and MiRP2 each form channels with Kv3.1-Kv3.2 heteromers that are kinetically distinct from one another and from MiRP/homomeric Kv3 channels. The findings illustrate a mechanism for dynamic expansion of the functional repertoire of Kv3.1 and Kv3.2 potassium currents and suggest roles for these alpha subunits outside the scope of sustained rapid neuronal firing.

Animals↗
PubMed2003

Syntaxin 1A co-associates with native rat brain and cloned large conductance, calcium-activated potassium channels in situ.

Large conductance, calcium-activated potassium channels (BKCa channels) are regulated by several distinct mechanisms, including phosphorylation/dephosphorylation events and protein-protein interactions. In this study, we have examined the interaction between BKCa channels and syntaxin 1A, a soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) that is reported to modulate the activity and/or localization of different classes of ion channels. Using a reciprocal co-immunoprecipitation strategy, we observed that native BKCa channels in rat hippocampus co-associate with syntaxin 1A, but not the closely related homologue syntaxin 3. This BKCa channel-syntaxin 1A interaction could be further demonstrated in a non-neuronal cell line (human embryonic kidney (HEK) 293 cells) following co-expression of rat syntaxin 1A and BKCa channels cloned from either mouse brain or bovine aorta. However, co-expression of these same channels with syntaxin 3 did not lead to a detectable protein-protein interaction. Immunofluorescent co-staining of HEK 293 cells expressing BKCa channels and syntaxin 1A demonstrated overlapping distribution of these two proteins in situ. Functionally, co-expression of BKCa channels with syntaxin 1A, but not syntaxin 3, was observed to enhance channel gating and kinetics at low concentrations (1-4 microM) of free cytosolic calcium, but not at higher concentrations (< or = 10 microM), as judged by macroscopic current recordings in excised membrane patches. Interactions between BKCa channels and neighbouring membrane proteins may thus play important roles in regulating the activity and/or distribution of these channels within specialized cellular compartments.

Animals↗
PubMed2001

Effect of ethanol on tracheal potassium channels reconstituted into bilayer lipid membranes.

We examined the effect of ethanol on single potassium channels derived from plasma membranes of bovine tracheal smooth muscles. The observed potassium channels had a conductance of 296 +/- 31 pS (mean +/- S.D.) in symmetrical 250 mmol/l KCl solutions, and exhibited a voltage- and Ca2+-dependence similar to BKCa channels. Ethanol at 50, 100 and 200 mM concentrations increased the probability of open potassium channels to 112 +/- 5, 127 +/- 7 and 121 +/- 13% (mean +/- S.E.M.), respectively. It is suggested that increased activity of the BKCa channels by ethanol hyperpolarizes the plasma membrane and thus may contribute to relaxation of tracheal smooth muscle.

Animals↗
PubMed2003

Stoichiometry of expressed KCNQ2/KCNQ3 potassium channels and subunit composition of native ganglionic M channels deduced from block by tetraethylammonium.

KCNQ2 and KCNQ3 potassium-channel subunits can form both homomeric and heteromeric channels; the latter are thought to constitute native ganglionic M channels. We have tried to deduce the stoichiometric contributions of KCNQ2 and KCNQ3 subunits to currents generated by the coexpression of KCNQ2 and KCNQ3 cDNA plasmids in Chinese hamster ovary (CHO) cells, and to native M currents in dissociated rat superior cervical ganglion (SCG) neurons, by comparing the block of these currents produced by tetraethylammonium (TEA) with the block of currents generated by a tandem KCNQ3/2 construct. TEA concentration-inhibition curves against coexpressed KCNQ2 plus KCNQ3 currents, and against native M currents in SCG neurons from 6-week-old [postnatal day 45 (P45)] rats, were indistinguishable from those for the expressed tandem construct, and fully accorded with a 1:1 stoichiometry. Inhibition curves in neurons from younger (P17) rats could be better fitted assuming an additional small proportion of current carried by KCNQ2 homomultimers. Single-cell PCR yielded signals for KCNQ2, KCNQ3, and KCNQ5 mRNAs in all SCG neurons tested from both P17 and P45 rats. Quantitative PCR of whole-ganglion mRNA revealed stable levels of KCNQ2 and KCNQ5 mRNA between P7 and P45, but excess and incrementing levels of KCNQ3 mRNA. Increasing levels of KCNQ3 protein between P17 and P45 were confirmed by immunocytochemistry. We conclude that coexpressed KCNQ2 plus KCNQ3 cDNAs generate channels with 1:1 (KCNQ2:KCNQ3) stoichiometry in CHO cells and that native M channels in SCG neurons adopt the same conformation during development, assisted by the increased expression of KCNQ3 mRNA and protein.

Animals↗
PubMed2000

Adenosine triphosphate-dependent potassium channel modulation and cardioplegia-induced protection of human atrial muscle in an in vitro model of myocardial stunning.

OBJECTIVES: Although adenosine triphosphate-dependent potassium channel openers have been shown to enhance cardioplegic protection in animal myocardium, there is a lack of data on human cardiac tissues. We aimed at determining, on human atrial muscle, whether adenosine triphosphate- dependent potassium channels are involved in protection caused by high-potassium cardioplegia and whether adenosine triphosphate-dependent potassium channel activation might improve cardioplegic protection in an in vitro model of myocardial stunning. METHODS: Human atrial trabeculae were obtained from adult patients undergoing cardiac operations. In an organ bath at 37 degrees C, the preparations were subjected to 60 minutes of hypoxia at a high stimulation rate either in Tyrode solution (control, n = 17) or in St Thomas' Hospital solution without additives (n = 6) or associated with 100 nmol/L bimakalim (n = 7) or 1 micromol/L glibenclamide (n = 7), followed by 60 minutes of reoxygenation and 15 minutes of positive inotropic stimulation with 1 micromol/L dobutamine. RESULTS: Atrial developed tension was reduced by hypoxia to 27% +/- 5% of baseline and incompletely recovered after reoxygenation to 38% +/- 7%, whereas dobutamine restored contractility to 74% +/- 7% of basal values. St Thomas' Hospital solution with or without bimakalim improved developed tension after reoxygenation and dobutamine (P <.0001 vs control), whereas glibenclamide inhibited these protective effects of cardioplegic arrest (P =.001 vs St Thomas' Hospital solution). After reoxygenation, the protective effect of bimakalim disappeared at a high pacing rate (400- and 300-ms cycle length) but recovered during dobutamine superfusion. CONCLUSIONS: Adenosine triphosphate-dependent potassium channels are likely involved in the cardioprotective effects of cardioplegia in human atrial trabeculae and adenosine triphosphate-dependent potassium channel activation with bimakalim used as an additive to cardioplegia enhanced protection.

Adenosine Triphosphate↗
PubMed2006

Ion pore properties of ionotropic glutamate receptors are modulated by a transplanted potassium channel selectivity filter.

The canonical potassium channel selectivity filter motif TVGYG was transplanted into ionotropic glutamate receptors (iGluRs) of the AMPA and NMDA subtype to test whether it renders the iGluRs K(+) selective. The TVGYG motif modulated several ion pore properties of AMPA receptor as well as NMDA receptor mutants, e.g., the intra- and extracellular polyamine block, current/voltage relationships, open channel block by MK801 and Mg(2+), and permeability for divalent cations. However, introduction of the selectivity filter failed to increase the K(+) selectivity of homomeric AMPA and heteromeric NMDA receptor complexes, which may be due to absence of selectivity filter-stabilizing interaction sites in the iGluR pore domain. Our findings indicate that even if glutamate receptors appear to have the intrinsic capacity for K(+) permeability, as is demonstrated by the prokaryotic, glutamate-gated, K(+) selective GluR0, the isolated selectivity filter is not able to confer K(+) permeability to the relatively unselective iGluR cation pore.

Animals↗
PubMed2003

Di-substituted cyclohexyl derivatives bind to two identical sites with positive cooperativity on the voltage-gated potassium channel, K(v)1.3.

Di-substituted cyclohexyl (DSC) derivatives inhibit the voltage-gated potassium channel, K(v)1.3, and have immunosuppressant activity (Schmalhofer et al. (2002) Biochemistry 41, 7781-7794). This class of inhibitors displays Hill coefficients of near 2 in functional assays, and trans DSC analogues appear to selectively interact with K(v)1.3 channel conformations related to C-type inactivation. To further understand the details of the DSC inhibitor interaction with potassium channels, trans-1-(N-n-propylcarbamoyloxy)-4-phenyl-4-(3-(2-methoxyphenyl)-3-oxo-2-azaprop-1-yl)cyclo-hexane (trans-NPCO-DSC) was radiolabeled with tritium, and its binding characteristics to K(v)1.3 channels were determined. Specific binding of [(3)H]-trans-NPCO-DSC to K(v)1.3 channels is a saturable, time-dependent, and fully reversible process. Saturation binding isotherms and competition binding experiments are consistent with the presence of two receptor sites for DSC derivatives on the K(v)1.3 channel that display positive allosteric cooperativity. The high affinity interaction of [(3)H]-trans-NPCO-DSC with K(v)1.3 channels appears to correlate with the rates of C-type inactivation of the channel. These data, taken together, mark the first demonstration of the existence of multiple binding sites for an inhibitor of an ion channel and suggest that the high affinity interaction of trans-NPCO-DSC and similar inhibitors with K(v)1.3 channels could be exploited for the development of selective molecules that target this protein.

Aza Compounds↗
PubMed1994

Activation of the cloned muscarinic potassium channel by G protein beta gamma subunits.

Acetylcholine released during parasympathetic stimulation of the vagal nerve slows the heart rate through the activation of muscarinic receptors and subsequent opening of an inwardly rectifying potassium channel. The activation of these muscarinic potassium channels is mediated by a pertussis toxin-sensitive heterotrimeric GTP-binding protein (G protein). It has not been resolved whether exogenously applied G alpha or G beta gamma, or both, activate the channel. Using a heterologous expression system, we have tested the ability of different G protein subunits to activate the cloned muscarinic potassium channel, GIRK1. We report here that coexpression of GIRK1 with G beta gamma but not G alpha beta gamma in Xenopus oocytes results in channel activity that persists in the absence of cytoplasmic GTP. This activity is reduced by fusion proteins of the beta-adrenergic receptor kinase and of recombinant G alpha i-GDP, both of which are known to interact with G beta gamma. Moreover, application of recombinant G beta gamma, but not G alpha i-GTP-gamma S, activates GIRK1 channels. Thus G beta gamma appears to be sufficient for the activation of GIRK1 muscarinic potassium channels.

Amino Acid Sequence↗
PubMed1998

dSLo interacting protein 1, a novel protein that interacts with large-conductance calcium-activated potassium channels.

Large-conductance calcium-activated potassium channels (BK channels) are activated by depolarized membrane potential and elevated levels of intracellular calcium. BK channel activity underlies the fast afterhyperpolarization that follows an action potential and attenuates neurotransmitter and hormone secretion. Using a modified two-hybrid approach, the interaction trap, we have identified a novel protein from Drosophila, dSLIP1 (dSLo interacting protein), which specifically interacts with Drosophila and human BK channels and has partial homology to the PDZ domain of alpha1 syntrophin. The dSLIP1 and dSlo mRNAs are expressed coincidently throughout the Drosophila nervous system, the two proteins interact in vitro, and they may be coimmunoprecipitated from transfected cells. Coexpression of dSLIP1 with dSlo or hSlo BK channels in Xenopus oocytes results in reduced currents as compared with expression of BK channels alone; current amplitudes may be rescued by coexpression with the channel domain that interacts with dSLIP1. Single-channel recordings and immunostaining of transfected tissue culture cells suggest that dSLIP1 selectively reduces Slo BK currents by reducing the number of BK channels in the plasma membrane.

Amino Acid Sequence↗
PubMed2002

Opening of potassium channels modulates mitochondrial function in rat skeletal muscle.

We have investigated the presence of diazoxide- and nicorandil-activated K+ channels in rat skeletal muscle. Activation of potassium transport in the rat skeletal muscle myoblast cell line L6 caused a stimulation of cellular oxygen consumption, implying a mitochondrial effect. Working with isolated rat skeletal muscle mitochondria, both potassium channel openers (KCOs) stimulate respiration, depolarize the mitochondrial inner membrane and lead to oxidation of the mitochondrial NAD-system in a strict potassium-dependent manner. This is a strong indication for KCO-mediated stimulation of potassium transport at the mitochondrial inner membrane. Moreover, the potassium-specific effects of both diazoxide and nicorandil on oxidative phosphorylation in skeletal muscle mitochondria were completely abolished by the antidiabetic sulfonylurea derivative glibenclamide, a well-known inhibitor of ATP-regulated potassium channels (K(ATP) channels). Since both diazoxide and nicorandil facilitated swelling of de-energised mitochondria in KSCN buffer at the same concentrations, our results implicate the presence of a mitochondrial ATP-regulated potassium channel (mitoK(ATP) channel) in rat skeletal muscle which can modulate mitochondrial oxidative phosphorylation.

Animals↗
PubMed1994

Activation of ATP-sensitive potassium channels lowers threshold for ischemic preconditioning in dogs.

The purpose of the present study was to determine whether enhanced activation of myocardial ATP-dependent potassium channels (KATP) with a potassium channel opener, bimakalim, can reduce the time necessary to produce the protective effect of ischemic preconditioning and to determine whether this effect is mediated via accelerating the rate of action potential shortening during preconditioning. Barbital-anesthetized dogs were subjected to 60 min of left anterior descending coronary artery (LAD) occlusion followed by 4 h of reperfusion. Ten minutes of preconditioning was found to markedly reduce myocardial infarct size from 30.6 +/- 4.7 to 7.1 +/- 2.6%. Subsequently, it was observed that either 3 min of LAD occlusion or a 3-min intracoronary infusion with 0.3 micrograms/min of bimakalim did not reduce myocardial infarct size. However, intracoronary infusion with bimakalim during the 3-min preconditioning period markedly reduced myocardial infarct size to a similar extent as that of ischemic preconditioning (12.2 +/- 1.9%). In addition, it was observed that bimakalim markedly accelerated the ischemia-induced shortening of the action potential during preconditioning. These results are the first to demonstrate that activation of KATP channels with a potassium channel opener reduces the threshold of time necessary to produce preconditioning in anesthetized dogs. These data also suggest that KATP channel activation may produce this effect by enhancing the rate of ischemic myocardial action potential shortening during preconditioning.

Action Potentials↗
PubMed2000

Patch-clamp analysis of anesthetic interactions with recombinant SK2 subtype neuronal calcium-activated potassium channels.

UNLABELLED: Small conductance calcium-activated potassium channels (SK) mediate spike frequency adaptation and underlie the slow afterhyperpolarization in central neurons. We tested the actions of several anesthetics on the SK2 subtype of recombinant SK channels, cloned from rat brain and functionally expressed in a mammalian cell line. Butanol, ethanol, ketamine, lidocaine, and methohexital blocked recombinant SK2 channel currents, measured in the whole-cell patch clamp recording mode. The block was reversible, dose-dependent, and of variable efficacy. The inhaled anesthetics chloroform, desflurane, enflurane, halothane, isoflurane, and sevoflurane produced little or no block when applied at 1 minimum alveolar anesthetic concentration; varying degrees of modulation were observed at very large concentrations (10 minimum alveolar concentration). The extent of block by inhaled anesthetics did not appear to depend on concentration or membrane voltage. IMPLICATIONS: We describe differential effects of anesthetics on cloned small conductance calcium-activated potassium channels from brain that may play a role in generating the effects or side effects of anesthetics.

Anesthetics↗
PubMed2000

Structural basis for the biological activity of dendrotoxin-I, a potent potassium channel blocker.

A topochemical model to explain the biological activity of dendrotoxin-I (DTX-I), a potent blocker for potassium channels, was developed by searching common spatial arrangements of functionally important residues between DTX-I, alpha-dendrotoxin, dendrotoxin-K, BgK, ShK, and charybdotoxin. The first three are structurally and functionally related to one another, and specifically target to Kv1 type potassium channels. The last three are structurally unrelated to the first three but have the ability to displace (125)I-labeled dendrotoxins on the same types of potassium channels. In order to obtain the correct electronic surface potential, thought to be crucial for the DTX-I function, we determined the three-dimensional solution structure of DTX-I by nmr spectroscopy using its correct amino acid sequence recently determined by our group. The most interesting characteristic of our model is that DTX-I has two binding sites to potassium channels: one is the cationic domain made up of Lys residues at positions 5 in the 3(10)-helix, 28 and 29 in the beta-turn, and the other is the Lys19/Tyr17/Trp37 triad located in the antiprotease domain. The cationic domain and the triad are located at the opposite sides of the molecular structure and are separated by about 25 A between Lys29 Calpha and Tyr17 Calpha. The functional triad is characterized by three distances, d(1) approximately 7.5 A (Lys19 Calpha-the center of the Tyr17 aromatic ring), d(2) approximately 8.1 A (Lys19 Calpha-the center of the 6-membered ring of the Trp37 indole group), and d(3) approximately 7. 3 A (the center of the Tyr17 aromatic ring-the center of the 6-membered ring of the Trp37 indole group). This model should aid in the pharmaceutical design of peptide and nonpeptide drugs with potassium channel blocking potencies, as well as in understanding of the physiology, pharmacology, biochemistry, and structure-function analysis of potassium channels.

Amino Acid Sequence↗