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 1,009 records · Page 56Linked to original sources
PubMed2001

Unitary conductance variation in Kir2.1 and in cardiac inward rectifier potassium channels.

Kir2.1 (IRK1) is the complementary DNA for a component of a cardiac inwardly rectifying potassium channel. When Kir2.1 is expressed in Xenopus oocytes or human embryonic kidney (HEK) cells (150 mM external KCl), the unitary conductances form a broad distribution, ranging from 2 to 33 pS. Channels with a similarly broad distribution of unitary conductance amplitudes are also observed in recordings from adult mouse cardiac myocytes under similar experimental conditions. In all three cell types channels with conductances smaller, and occasionally larger, than the ~30 pS ones are found in the same patches as the ~30 pS openings, or in patches by themselves. The unitary conductances in patches with a single active channel are stable for the durations of the recordings. Channels of all amplitudes share several biophysical characteristics, including inward rectification, voltage sensitivity of open probability, sensitivity of open probability to external divalent cations, shape of the open channel i-V relation, and Cs(+) block. The only biophysical difference found between large and small conductance channels is that the rate constant for Cs(+) block is reduced for the small-amplitude channels. The unblocking rate constant is similar for channels of different unitary conductances. Apparently there is significant channel-to-channel variation at a site in the outer pore or in the selectivity filter, leading to variability in the rate at which K(+) or Cs(+) enters the channel.

Animals↗
PubMed2007

Relaxation of human placental arteries and veins by ATP-sensitive potassium channel openers.

BACKGROUND: Adenosine triphosphate (ATP)-sensitive potassium channels (K(ATP)) are important modulators of vascular tone. Preliminary data from our laboratory suggests that K(ATP) channels are expressed in the fetoplacental vasculature where addition of pinacidil, a specific K(ATP) opener, promotes relaxation. We aimed to assess the effects of KRN2391 and KRN4884 on the fetoplacental vasculature, which are putative K(ATP) channel openers. MATERIALS AND METHODS: Functional activity of K(ATP) channels was assessed in chorionic plate arteries and veins using wire myography. Cromakalim-, KRN2391- and KRN4884-induced relaxations were assessed in the presence and absence of agonist-induced pretone. Cromakalim, an established K(ATP) channel opener, acted as control. RESULTS: KRN2391 evoked significantly greater relaxation of chorionic plate arteries and veins than either KRN4884 or cromakalim. KRN2391-induced relaxation of precontracted arteries and veins was reduced in the presence of inhibitors of the nitric oxide pathway (L-NNA or LY83583). With KRN4884, there was no contribution of nitric oxide to the induced relaxation. CONCLUSIONS: We conclude that K(ATP) channels play an important role in controlling placental vascular tone. KRN2391 induces relaxation of human placental blood vessels by activation of K(ATP) channels and via activation of nitric oxide-dependent pathways.

Adenosine Triphosphate↗
PubMed1991

Potassium channel blockers: could they work in Alzheimer disease?

Many of the actions of potassium channel blockers, such as 4-aminopyridine, appear to complement the deficits in Alzheimer disease. The two clinical studies in the literature are contradictory, so potassium channel blockers may still merit trial in Alzheimer disease.

4-Aminopyridine↗
PubMed2004

Rapid intracellular TEA block of the KcsA potassium channel.

Intracellular tetraethylammonium (TEA) inhibition was studied at the single-channel level in the KcsA potassium channel reconstituted in planar lipid bilayers. TEA acts as a fast blocker (resulting in decreased current amplitude) with an affinity in the 75 mM range even at high bandwidth. Studies over a wide voltage range reveal that TEA block has a complex voltage-dependence that also depends on the ionic conditions. These observations are examined in the context of permeation models to extend our understanding of the coupling between permeant ions and TEA blockade.

Bacterial Proteins↗
PubMed2002

Effects of ATP-sensitive potassium channel openers on the contractile and phosphatidylinositol responses of the rat trachea.

PURPOSE: Although ATP-sensitive potassium channel openers suppress airway smooth muscle contraction, their potencies are different and the mechanisms involved are not fully understood. We examined the effects of cromakalim and Y-26763, a novel ATP-sensitive potassium channel opener, on the contractile and phosphatidylinositol responses of the rat trachea. METHODS: Thirty-six male Wistar rats, weighing 250-350 g, were used. In the experiment on contractile response, active contraction was induced with 0.55 microM carbachol in the presence or absence of cromakalim or Y-26763. In the experiment on phosphatidylinositol response, the tracheal slices were incubated with [(3)H] myo-inositol, 0.55 microM carbachol, and cromakalim or Y-26763, and the formation of [(3)H]inositol monophosphate (IP(1)), a degradation product of phosphatidylinositol response, was measured with a liquid scintillation counter. Statistical significance ( P < 0.05) was determined by analysis of variance (ANOVA). RESULTS: Carbachol-induced tension was attenuated by both cromakalim and Y-26763, the latter displaying significantly greater potency. Carbachol-induced IP(1) accumulation was influenced neither by cromakalim nor by Y-26763. CONCLUSION: Both cromakalim and Y-26763 have effects on airway smooth muscle relaxation. Carbachol-induced IP(1) accumulation was influenced neither by cromakalim nor by Y-26763, suggesting that phosphatidylinositol response may not be a common pathway for the effect of ATP-sensitive potassium channel openers.

Journal Article↗
PubMed1993

[Changes in endocochlear potential induced by potassium-channel blockers].

The effect of various potassium-channel blockers, 4-aminopyridine (4-AP), tetraethylammonium (TEA) and quinine, on the endocochlear potential (EP) was studied in perfused guinea pig inner ears. The fast K(+)-channel blocker, 4-AP, did not alter EP but changed its response model to intense noise exposure. While TEA and quinine significantly reduced the amplitude of negative component of EP (N-EP), comparing with a relatively smaller increase in general EP (G-EP). The results indicated the existence of different K(+)-channels with different physiological functions.

4-Aminopyridine↗
PubMed1988

Subset-specific expression of potassium channels in developing murine T lymphocytes.

Ion channels were studied in four major subsets of developing murine thymocytes by using patch-clamp recording and cell-surface staining techniques. The expression of three types of voltage-gated potassium channels in thymocytes varies consistently with the cell's developmental state and functional class as defined by cell-surface markers. One class of potassium channel (type n) predominates in immature thymocyte subsets as well as in mature-phenotype CD4+CD8- thymocytes (precursors to helper T lymphocytes), and the average surface density of this channel type correlates with the extent of cell proliferation. Two additional types of potassium channels (types n' and l) are found in the mature CD4-CD8+ thymocyte subset that contains precursors to cytotoxic and suppressor T cells. The subset-specific expression of type n' and l potassium channels suggests their use as additional cell-surface markers with which to identify precursors to the cytotoxic suppressor T cell lineage.

Animals↗
PubMed1996

Kv2.1 and electrically silent Kv6.1 potassium channel subunits combine and express a novel current.

Heteromultimer formation between Kv potassium channel subfamilies with the production of a novel current is reported for the first time. Protein-protein interactions between Kv2.1 and electrically silent Kv6.1 alpha-subunits were detected using two microelectrode voltage clamp and yeast two-hybrid measurements. Amino terminal portions of Kv6.1 were unable to form homomultimers but interacted specifically with amino termini of Kv2.1. Xenopus oocytes co-injected with Kv6.1 and Kv2.1 cRNAs exhibited a novel current with decreased rates of deactivation, decreased sensitivity to TEA block, and a hyperpolarizing shift of the half maximal activation potential when compared to Kv2.1. Our results indicate that Kv channel subfamilies can form heteromultimeric channels and, for the first time, suggest a possible functional role for the Kv6 subfamily.

Animals↗
PubMed2003

Tight coupling of rubidium conductance and inactivation in human KCNQ1 potassium channels.

KCNQ1 K+ channels in humans are important for repolarization of cardiac action potentials and for K+ secretion in the inner ear. The pore-forming channel subunits form heteromeric complexes with small regulatory subunits of the KCNE family, in particular with KCNE1 to form channels that conduct a slow delayed rectifier K+ current, IKs. This association leads to alteration of biophysical properties, including a slowing of activation, a suppression of inactivation and an increase of the apparent single-channel conductance. In addition, inward Rb+ currents conducted by homomeric KCNQ1 channels are about threefold larger than K+ currents, whereas heteromeric KCNQ1-KCNE1 channels have smaller inward Rb+ currents compared to K+ currents. We determined inactivation properties and compared K+ vs. Rb+ inward currents for channels formed by co-assembly of KCNQ1 with KCNE1, KCNE3 and KCNE5, and for homomeric KCNQ1 channels with point mutations in the pore helix S5 or S6 transmembrane domains. Several of the channels with point mutations eliminated the apparent inactivation of KCNQ1, as described previously (Seebohm et al. 2001). We found that the extent of inactivation and the ratio of Rb+/K+ currents were positively correlated. Since the effect of Rb+ on the current size has been shown previously to be related to a fast 'flickery' process, our results suggest that inactivation of KCNQ1 channels is related to a fast flicker of the open channel. A kinetic model incorporating two open states, no explicit inactivated state and a fast flicker that is different for the two open states is able to account for the apparent inactivation and the correlation of inactivation and large Rb+ currents. We conclude that an association between KCNQ1 and KCNE subunits or removal of inactivation by mutation of KCNQ1 stabilizes the open conformation of the pore principally by altering an interaction between the pore helix and the selectivity filter and with S5/S6 domains.

Action Potentials↗
PubMed1998

The effects of nucleotides and potassium channel openers on the SUR2A/Kir6.2 complex K+ channel expressed in a mammalian cell line, HEK293T cells.

The effects of potassium channel opening drugs and intracellular nucleotides on the ATP-sensitive K+ (KATP) channel composed of SUR2A and Kir6.2 in HEK293T cells were examined using the patch-clamp technique. The SUR2A/Kir6.2 channel was activated effectively by pinacidil, marginally by nicorandil but not by diazoxide. The pinacidil-activated channel currents were inhibited by glibenclamide with a Ki value of 160 nM. Upon formation of inside-out (I-O) patches, spontaneous openings of the channels appeared, which were inhibited by intracellular ATP (ATPi) equipotently in the presence and in the absence of intracellular Mg2+ (Mg2+i). The channel activity ran-down gradually in I-O patches. The run-down channels could be reactivated by ATPi only in the presence of Mg2+i. Uridine 5'-diphosphate (UDP) antagonized the ATPi-mediated inhibition of the channel activity before run-down. After run-down, UDP activated the channel without antagonizing ATPi-mediated channel inhibition. Thus, the SUR2A/Kir6.2 reproduced the major properties of the native cardiac KATP channel well in terms of nucleotide regulation and pharmacology, and therefore can be a useful tool with which to elucidate the molecular mechanisms characterizing the KATP channel.

ATP-Binding Cassette Transporters↗
PubMed1989

Potassium channels from NG108-15 neuroblastoma-glioma hybrid cells. Primary structure and functional expression from cDNAs.

The complete amino acid sequences of two potassium channel proteins from NG108-15 neuroblastoma-glioma hybrid cells have been deduced by cloning and sequencing the cDNAs. One of these proteins (NGK2) is structurally more closely related to the Drosophila Shaw gene product than to the Shaker and Shab gene products, whereas the other (NGK1) is identical with a rat brain potassium channel protein (BK2) which is more closely related to the Drosophila Shaker gene product. mRNAs derived from both the cloned cDNAs, when injected into Xenopus oocytes, direct the formation of functional potassium channels with properties of delayed rectifiers.

Amino Acid Sequence↗
PubMed1992

Different mechanisms of relaxation of pig coronary artery to bradykinin and cromakalim are distinguished by potassium channel blockers.

Bradykinin relaxes porcine coronary artery in an endothelium-dependent manner that is not dependent on release of nitric oxide or cyclic GMP accumulation. The mechanism of this relaxation was investigated in rings of porcine coronary artery by comparing bradykinin-induced relaxation with that induced by cromakalim, an agent know to cause hyperpolarization mediated by potassium channels. Relaxation to bradykinin was determined in rings treated with methylene blue, indomethacin and captopril to inhibit cyclic GMP accumulation, prostaglandin formation and bradykinin degradation, respectively. Relaxation to cromakalim was inhibited by the potassium channel blockers glybenclamide (10(-6) M), tetraethylammonium (10(-2) M), quinine (3 x 10(-5) M) and procaine (5 x 10(-3) M), whereas barium (10(-4) M) and 4-amino-pyridine (10(-3) M) were without effect. None of these potassium channel blockers had any effect on the relaxation to bradykinin. These results suggest that relaxation of pig coronary artery to cromakalim is mediated by a mechanism sensitive to potassium channel blockers. Also, the mechanism of nitric oxide-independent relaxation to bradykinin is distinct from that of cromakalim.

4-Aminopyridine↗
PubMed2000

Regulation of the cardiac repolarizing HERG potassium channel by protein kinase A.

Protein kinase A is an enzyme that regulates many cellular processes and is activated in many pathological conditions such as stress and various types of heart failure. Recently it has been shown that protein kinase A couples functionally to the HERG cardiac potassium channel, thereby altering repolarization in the heart. This link between a repolarizing potassium channel and the protein kinase system of cardiac cells may contribute to arrhythmogenesis and may become a target for future approaches to antiarrhythmic therapy.

Animals↗
PubMed1992

Structure and regulation of the MinK potassium channel.

MinK is a novel protein which induces an extremely slowly activating potassium channel when expressed in Xenopus oocytes. We discuss the properties and regulation of the current and localization and possible physiological roles of the MinK protein.

Amino Acid Sequence↗
PubMed1989

Pentylenetetrazole-induced changes of the single potassium channel in primary cultured cerebral cortical neurons.

To elucidate the behavior of the single ionic channels of cerebral cortical neurons during bursting activity, the effects of pentylenetetrazole (PTZ) on a single potassium channel of primary cultured cerebral cortical neurons from mice were examined. All of the examined 10-day-old primary cultured neurons of the cerebral cortex showed clear bursting activity after extracellular application of PTZ using whole-cell patch-clamp recording. Less than half of the examined single potassium channels, both outward and inward, of the 2- and 3-day-old as well as 6-10-day-old primary cultured cerebral cortical neurons showed the bursting-type open-close state by application of PTZ. The PTZ-sensitive single potassium channels were found in the voltage-dependent as well as calcium-activated channels.

Animals↗
PubMed2000

Potassium channels: molecular defects, diseases, and therapeutic opportunities.

Potassium channels play important roles in vital cellular signaling processes in both excitable and nonexcitable cells. Over 50 human genes encoding various K(+) channels have been cloned during the past decade, and precise biophysical properties, subunit stoichiometry, channel assembly, and modulation by second messenger and ligands have been elucidated to a large extent. Recent advances in genetic linkage analysis have greatly facilitated the identification of many disease-producing loci, and naturally occurring mutations in various K(+) channels have been identified in diseases such as long-QT syndromes, episodic ataxia/myokymia, familial convulsions, hearing and vestibular diseases, Bartter's syndrome, and familial persistent hyperinsulinemic hypoglycemia of infancy. In addition, changes in K(+) channel function have been associated with cardiac hypertrophy and failure, apoptosis and oncogenesis, and various neurodegenerative and neuromuscular disorders. This review aims to 1) provide an understanding of K(+) channel function at the molecular level in the context of disease processes and 2) discuss the progress, hurdles, challenges, and opportunities in the exploitation of K(+) channels as therapeutic targets by pharmacological and emerging genetic approaches.

Alzheimer Disease↗
PubMed1995

Dynamic modification of dendritic cable properties and synaptic transmission by voltage-gated potassium channels.

Computer simulations of a dendrite possessing voltage-sensitive potassium conductances were used to determine the effects of these conductances on synaptic transmission and on the propagation of synaptic signals within the dendritic tree. Potassium conductances had two principal effects on voltage transients generated by current injections or synaptic conductances. Locally (near the source of the transient), voltage-gated potassium channels produced a potassium shunt current that reduced the amplitude of voltage transient increased and so acted to prevent large synaptic transients from reaching levels that would saturate due to a reduction in driving force. In the presence of rapidly activating potassium currents, excitatory synapses produced larger synaptic currents that were more linearly related to synaptic conductance, but these produced smaller voltage transients. The maximum amplitudes of the voltage transients were limited by the voltage sensitivity of the K+ conductance and the rate at which it could activate. Sufficiently rapid synaptic currents could outrun the K+ conductance and thus achieve high local peak amplitudes. These effects of K+ conductances were unrelated to whether they were located on dendrites or not, being related only to their proximity to the source of synaptic current. The second class of effects of K+ conductances depended on their alteration of the electronic structure of the postsynaptic cell and so were observed only when they were located on postsynaptic dendrites. Voltage-gated K+ conductances produced voltage-dependent electronic expansion of depolarized dendrites, which had the effect of isolating synaptic inputs on depolarized dendrites from events on the rest of the neuron. Thus, synapses on the same dendrite interacted destructively to a degree much greater than that expected from the classical driving force nonlinearity. Synapses located proximally to a depolarized dendritic region were less effected than those located distally, and the range of the nonlinear interaction between synapses was dependent on the kinetics of activation and deactivation of the conductance. When present in conjunction with rapidly activating dendritic sodium conductance, the potassium conductance sharpened the requirement for spatial and temporal coincidence to produce synaptic boosting by inward currents, and suppressed out-of-synchrony synaptic inputs.

Computer Simulation↗
PubMed1993

Potassium channels as pharmacological targets in cardiovascular medicine.

Potassium channels are membrane receptor sites for various drugs in the field of cardiovascular diseases. These channel proteins are extremely diverse, not only as regards their molecular structure but also as regards their function. Heterogeneous expression of various K+ channel subtypes is an integral part of cell specialization in different tissues. K+ channels interfere with most of the physiological processes of the cardiac muscle, of the vascular smooth muscle and of the endothelial cells. K+ channel blockers are antidiabetic agents but also antiarrhythmic drugs. K+ channel openers are used in the treatment of hypertension and most recently in the treatment of coronary heart disease. In the experimental setting, K+ channel openers afford cytoprotection during ischaemia. This exciting property opens a new field in clinical research.

Adenosine Triphosphate↗