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Results for “Delayed Rectifier Potassium Channels”

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PubMed2003

Strain-specific effects of acidic pH on contractile state of aortas from Wistar and Wistar Kyoto rats.

The effects of acidosis were investigated on the resting and precontracted aortas from Wistar and Wistar Kyoto (WKY) rats. Decrease in pH from 7.4 to 6.5, having no effect on the resting tension of Wistar aorta, induced a marked contraction of WKY aorta. Acidic pH markedly relaxed the contraction to 300 nM phenylephrine in Wistar aorta, whereas in WKY aorta, it produced a biphasic response, an initial relaxation followed by potentiation of the contraction. In aortas loaded with fura 2-AM, phenylephrine caused an increase in intracellular Ca2+ ([Ca2+]i) and a contraction in both Wistar and WKY rats. pH 6.5 produced a decrease in [Ca2+]i to a near-basal level and almost abolished the phenylephrine-induced contraction in Wistar rat aorta. However, in WKY aorta, a biphasic response, an initial decline and later a recovery of [Ca2+]i level, was observed. Interestingly, at similar sustained [Ca2+]i, the contractile response to phenylephrine in WKY aorta was potentiated under acidic pH conditions. Acidic pH-induced inhibition of the contraction to phenylephrine was unaffected by iberiotoxin, 4-aminopyridine, and glibenclamide (Ca2+-activated, delayed rectifier and ATP-sensitive K+ channel inhibitors, respectively), in aortas from both Wistar and WKY. Decrease in extracellular pH was associated with a rapid fall in intracellular pH (pHi) and the intracellular acidification profile was not different in both strains. All these results show that acidic pH induces strain-specific inhibitory and excitatory effects on the contractile state of aortas from Wistar and WKY rats, respectively. The sustained and transient relaxant responses to acidic pH in Wistar and WKY aortas, respectively, are due to decrease in [Ca2+]i levels, but this decrease in [Ca2+]i is independent of the activation of K+ channels.

Acidosis↗

PubMed2000

Regulation of Shaker-type potassium channels by hypoxia. Oxygen-sensitive K+ channels in PC12 cells.

Little is known about the molecular composition of the O2-sensitive K+ (Ko2) channels. The possibility that these channels belong to the Shaker subfamily (Kv1) of voltage-dependent K+ (Kv) channels has been raised in pulmonary artery (PA) smooth muscle cells. Numerous findings suggest that the Ko2 channel in PC12 cells is a Kv1 channel, formed by the Kv1.2 alpha subunit. The Ko2 channel in PC12 cells is a slow-inactivating voltage-dependent K+ channel of 20 pS conductance. Other Kv channels, also expressed in PC12 cells, are not inhibited by hypoxia. Selective up-regulation by chronic hypoxia of the Kv1.2 alpha subunit expression correlates with an increase O2-sensitivity of the K+ current. Other Kv1 alpha subunit genes encoding slow-inactivating Kv channels, such as Kv1.3, Kv2.1, Kv3.1 and Kv3.2 are not modulated by chronic hypoxia. The Ko2 current in PC12 cells is blocked by 5 mM externally applied tetraethylammonium chloride (TEA) and by charydbotoxin (CTX). The responses of the Kv1.2 K+ channel to hypoxia have been studied in the Xenopus oocytes and compared to those of Kv2.1, also proposed as Ko2 channel in PA smooth muscle cells. Two-electrode voltage clamp experiments show that hypoxia induces inhibition of K+ current amplitude only in oocytes injected with Kv1.2 cRNA. These data indicate that Kv1.2 K+ channels are inhibited by hypoxia.

Animals↗

PubMed2003

Comparison of the effect of class IA antiarrhythmic drugs on transmembrane potassium currents in rabbit ventricular myocytes.

BACKGROUND: The blockade of cardiac transmembrane potassium channels, which is commonly seen with various antiarrhythmic drugs, plays an important role in their mechanism of action. We studied and compared the less-explored effects of three Class IA antiarrhythmics on the transient outward current (I(to)) and on the inward rectifier (I(kl)), ATP sensitive (I(KATP)), and delayed rectifier (I(K)) potassium currents in rabbit ventricular myocytes. METHODS AND RESULTS: Transmembrane currents were measured by applying the whole-cell configuration of the patch-clamp technique at 37 degrees C in myocytes enzymatically isolated from rabbit ventricular preparations. Quinidine (10 microM), disopyramide (10 microM), and procainamide (50 microM) were studied at concentrations close to or exceeding the therapeutic plasma level. All studied drugs significantly decreased the amplitude of I(KATP) (activated by 50 microM pinacidil) and I(K) currents. None of them influenced significantly I(kl). The amplitude of I(to) was decreased by quinidine and disopyramide but was not considerably altered by procainamide. The fast inactivation of I(to) was not changed by procainamide and was significantly accelerated by quinidine and disopyramide. CONCLUSION: Although quinidine, disopyramide, and procainamide are all classified as Class IA antiarrhythmics, these drugs had different effects on various potassium currents, which may partially explain their distinct effect on repolarization in various cardiac tissues and on cardiac arrhythmias in clinical settings.

Adenosine Triphosphate↗

PubMed1998

A novel crystallization method for visualizing the membrane localization of potassium channels.

The high permeability of K+ channels to monovalent thallium (Tl+) ions and the low solubility of thallium bromide salt were used to develop a simple yet very sensitive approach to the study of membrane localization of potassium channels. K+ channels (Kir1.1, Kir2.1, Kir2.3, Kv2.1), were expressed in Xenopus oocytes and loaded with Br ions by microinjection. Oocytes were then exposed to extracellular thallium. Under conditions favoring influx of Tl+ ions (negative membrane potential under voltage clamp, or high concentration of extracellular Tl+), crystals of TlBr, visible under low-power microscopy, formed under the membrane in places of high density of K+ channels. Crystals were not formed in uninjected oocytes, but were formed in oocytes expressing as little as 5 microS K+ conductance. The number of observed crystals was much lower than the estimated number of functional channels. Based on the pattern of crystal formation, K+ channels appear to be expressed mostly around the point of cRNA injection when injected either into the animal or vegetal hemisphere. In addition to this pseudopolarized distribution of K+ channels due to localized microinjection of cRNA, a naturally polarized (animal/vegetal side) distribution of K+ channels was also frequently observed when K+ channel cRNA was injected at the equator. A second novel "agarose-hemiclamp" technique was developed to permit direct measurements of K+ currents from different hemispheres of oocytes under two-microelectrode voltage clamp. This technique, together with direct patch-clamping of patches of membrane in regions of high crystal density, confirmed that the localization of TlBr crystals corresponded to the localization of functional K+ channels and suggested a clustered organization of functional channels. With appropriate permeant ion/counterion pairs, this approach may be applicable to the visualization of the membrane distribution of any functional ion channel.

Animals↗

PubMed1999

Heterogeneous expression of voltage-gated potassium channels of the shaker family (Kv1) in oligodendrocyte progenitors.

Outwardly rectifying K(+) channels determine the membrane conductance and influence the proliferation rate of glial progenitor cells. To analyze the molecular identity and the functional role of K(+) channels in glial progenitors of mouse brain, expression of shaker-type Kv1 genes was studied at three levels: (1) presence of Kv1 mRNAs, (2) biosynthesis of channel proteins and (3) electrophysiological and pharmacological properties of K(+) currents. mRNA expression of Kv1.1 to Kv1.6 genes was studied by single-cell reverse transcription-mediated polymerase chain reaction (RT-PCR) using degenerate primers to amplify the six Kv1 transcripts. Most cells expressed several mRNA combinations simultaneously. In more than half of the cells, messages for Kv1.2, Kv1.5 and Kv1.6 were found, while Kv1.1, Kv1.3 and Kv1.4 were detected in only a minority of cells. In contrast, at the level of protein expression - employing immunocytochemistry with subtype-specific antibodies - Kv1. 2 and Kv1.3 were undetectable (<2%), while almost all cells expressed Kv1.4 (85%), Kv1.5 (99%) and Kv1.6 (99%). Kv1.1 was present in a minor cell population (10%). Functional contribution of Kv1 proteins to progenitor membrane conductance was determined by analyzing the voltage-dependence of K(+) current activation and inactivation as well as their current sensitivities to the subtype-preferring blockers and toxins tetraethylammonium (TEA), 4-aminopyridine (4-AP), charybdotoxin (CTX), alpha-dendrotoxin (DTX) and mast-cell degranulating peptide (MCDP). From these results, it is concluded: first, glial progenitor cells can express all transcripts of the six Kv1 genes, but do not express all proteins; second, Kv1.4, Kv1.5 and Kv1.6 proteins are most abundant and were found in the majority of cells; and third, K(+) currents flow predominantly either through heteromeric channel complexes or through homomeric Kv1.5 ion pores, but not through homomeric Kv1.4 or Kv1.6 channels.

Animals↗

PubMed1996

Single-channel analysis of a delayed rectifier K+ channel in Xenopus myelinated nerve.

Single-channel properties of a delayed rectifier voltage-gated K+ channel (I-type) were investigated in peripheral myelinated axons from Xenopus laevis. Channels activated between -60 and -40 mV with a potential of half-maximal activation, E50, at -47.5 mV. Averaged single-channel currents activated with a time delay at all membrane potentials tested. Time to half-maximal activation decreased from 80 to 1.6 msec between -60 and +40 mV. The channel inactivated monoexponentially with a time constant of 10.9 sec at -40 mV. The time constant of deactivation was 126 msec at -80 mV and 16.9 msec at -110 mV. In symmetrical 105 mM K+, the single-channel conductance (gamma) was 22 and 13 pS at negative and positive membrane potentials, respectively, at 13-15 degrees C. In Na+ -rich solution with 2.5 mM extracellular K+ gamma was 7 pS and the reversal potential was negative to -80 mV, indicating a high selectivity for K+ over Na+. gamma depended on extracellular K+ concentration (KD = 19.6 mM) and temperature (Q10 = 1.45). External tetraethylammonium (TEA) reduced the apparent single-channel amplitude at all potentials tested with a half-maximal inhibiting concentration (IC50) of 0.6 mM. Open probability of the channel, but not single-channel current amplitude was decreased by extracellular dendrotoxin (DTX, IC50 = 6.8 nM). mast cell degranulating peptide (MCDP, IC50 = 41.9 microM). In Ringer solution the membrane potential of macroscopic I-channel patches was about -65 mV and depolarized under TEA and DTX. It is concluded that besides their activation during action potentials, I-channels may also stabilize the resting membrane potential.

Animals↗

PubMed1994

Permeation of Na+ through a delayed rectifier K+ channel in chick dorsal root ganglion neurons.

In whole-cell patch clamp recordings from chick dorsal root ganglion neurons, removal of intracellular K+ resulted in the appearance of a large, voltage-dependent inward tail current (Icat). Icat was not Ca2+ dependent and was not blocked by Cd2+, but was blocked by Ba2+. The reversal potential for Icat shifted with the Nernst potential for [Na+]. The channel responsible for Icat had a cation permeability sequence of Na+ >> Li+ >> TMA+ > NMG+ (PX/PNa = 1:0.33:0.1:0) and was impermeable to Cl-. Addition of high intracellular concentrations of K+, Cs+, or Rb+ prevented the occurrence of Icat. Inhibition of Icat by intracellular K+ was voltage dependent, with an IC50 that ranged from 3.0-8.9 mM at membrane potentials between -50 and -110 mV. This voltage-dependent shift in IC50 (e-fold per 52 mV) is consistent with a single cation binding site approximately 50% of the distance into the membrane field. Icat displayed anomolous mole fraction behavior with respect to Na+ and K+; Icat was inhibited by 5 mM extracellular K+ in the presence of 160 mM Na+ and potentiated by equimolar substitution of 80 mM K+ for Na+. The percent inhibition produced by both extracellular and intracellular K+ at 5 mM was identical. Reversal potential measurements revealed that K+ was 65-105 times more permeant than Na+ through the Icat channel. Icat exhibited the same voltage and time dependence of inactivation, the same voltage dependence of activation, and the same macroscopic conductance as the delayed rectifier K+ current in these neurons. We conclude that Icat is a Na+ current that passes through a delayed rectifier K+ channel when intracellular K+ is reduced to below 30 mM. At intracellular K+ concentrations between 1 and 30 mM, PK/PNa remained constant while the conductance at -50 mV varied from 80 to 0% of maximum. These data suggest that the high selectivity of these channels for K+ over Na+ is due to the inability of Na+ to compete with K+ for an intracellular binding site, rather than a barrier that excludes Na+ from entry into the channel or a barrier such as a selectivity filter that prevents Na+ ions from passing through the channel.

Animals↗

PubMed1998

Delayed rectifier potassium currents induced in activated rat microglia set the resting membrane potential.

The delayed rectifying outward K+ (IK) current was measured in lipopolysaccharide (LPS)-activated cultured rat microglial cells by using whole-cell patch clamp method. The current showed 'window current' where channels were available for activation but never fully inactivated. At near resting membrane potential some part of the current was able to be activated by depolarization. Among the several K+ channel blockers tested, only 4-aminopyridine (4-AP) was able to block most of the current and depolarize the membrane potential reversibly. These results suggest that 4-AP sensitive IK current plays a direct role of setting the resting membrane potential in LPS-activated microglia.

4-Aminopyridine↗

PubMed1999

Inhibition of hKv2.1, a major human neuronal voltage-gated K+ channel, by meclofenamic acid.

Using the standard patch clamp whole cell recording method, we assessed the pharmacological activity of four fenamate nonsteroidal anti-inflammatory drugs, meclofenamic acid, flufenamic acid, mefenamic acid and niflumic acid, on hKv2.1, a major human neuronal voltage-gated potassium channel stably expressed heterologously in Chinese hamster ovary cells. Meclofenamic acid inhibited hKv2.1 in a concentration-dependent manner whereas the other three fenamates had weaker or no effect on these channels at a concentration of 100 microM. The estimated IC50 of meclofenamic acid was 56.0 microM for hKv2.1 compared an IC50 of 155.9 microM for another human neuronal K channel (hKv1.1). Meclofenamic acid reached its maximum inhibition within 5 min of bath application and its effect was readily reversed upon wash. Kinetic analysis revealed that this drug did not alter the channel activation or deactivation time courses. Moreover, the effect of meclofenamic acid on hKv2.1 channels was not voltage-dependent. Indomethacin, another inhibitor of the cyclooxygenase that catalyses the synthesis of prostaglandin from arachidonic acid, had no effect on either hKv2.1 or hKv1.1. These results indicate that meclofenamic acid inhibits hKv2.1 more potently than hKv1.1 and it is likely that this compound acts directly on the channel proteins.

Animals↗

PubMed2001

Modulation of outward potassium currents in aligned cultures of neonatal rat ventricular myocytes during phorbol ester-induced hypertrophy.

Protein kinase C-stimulating phorbol esters induce a strong hypertrophic response when applied in vitro to cardiac ventricular myocytes. The aim of this study was to determine if this in vitro model of hypertrophy is associated with changes in the expression of voltage-gated K(+)channels. Myocytes were isolated from 3--4-day-old neonatal rats and cultured on aligned collagen thin gels. Membrane currents were measured with the use of the whole-cell arrangement of the patch clamp technique and the expression levels of the Kv1.4, Kv4.2 and Kv2.1 alpha subunits quantified using Western blot analysis. Voltage steps positive to -30 mV resulted in the activation of both a transient (I(to)) and a sustained (I(sus)) component of outward K(+)current in the aligned myocytes. Overnight exposure to phorbol 12-myristate 13-acetate (PMA) caused a 55% increase in myocyte size and a three-fold reduction in the peak amplitude of I(to). No differences in the half-maximal voltages required for activation and steady-state inactivation were observed between I(to)measured in control and PMA-treated myocytes. In contrast, PMA treatment resulted in a 62% increase in a tetraethylammonium-sensitive component of I(sus)(TEA-I(sus)) and was associated with the appearance of a slow component of current decay. Expression levels of the Kv1.4 and Kv4.2 alpha subunits were strongly depressed in the hypertrophic myocytes, while the density of the Kv2.1 alpha subunit was enhanced. PMA-induced changes in the Kv alpha subunits were partially prevented through inhibition of the mitogen-activated protein kinase (MAPK) pathway. Thus, PMA-induced hypertrophy of cultured ventricular myocytes is associated with an altered expression of voltage-gated K(+)channels.

Animals↗

PubMed1999

Identification of the Kv2.1 K+ channel as a major component of the delayed rectifier K+ current in rat hippocampal neurons.

Molecular cloning studies have revealed the existence of a large family of voltage-gated K+ channel genes expressed in mammalian brain. This molecular diversity underlies the vast repertoire of neuronal K+ channels that regulate action potential conduction and neurotransmitter release and that are essential to the control of neuronal excitability. However, the specific contribution of individual K+ channel gene products to these neuronal K+ currents is poorly understood. We have shown previously, using an antibody, "KC, " specific for the Kv2.1 K+ channel alpha-subunit, the high-level expression of Kv2.1 protein in hippocampal neurons in situ and in culture. Here we show that KC is a potent blocker of K+ currents expressed in cells transfected with the Kv2.1 cDNA, but not of currents expressed in cells transfected with other highly related K+ channel alpha-subunit cDNAs. KC also blocks the majority of the slowly inactivating outward current in cultured hippocampal neurons, although antibodies to two other K+ channel alpha-subunits known to be expressed in these cells did not exhibit blocking effects. In all cases the blocking effects of KC were eliminated by previous incubation with a recombinant fusion protein containing the KC antigenic sequence. Together these studies show that Kv2.1, which is expressed at high levels in most mammalian central neurons, is a major contributor to the delayed rectifier K+ current in hippocampal neurons and that the KC antibody is a powerful tool for the elucidation of the role of the Kv2.1 K+ channel in regulating neuronal excitability.

Animals↗

PubMed1997

Presynaptic recordings from Drosophila: correlation of macroscopic and single-channel K+ currents.

We have performed direct electrophysiological recordings from Drosophila peptidergic synaptic boutons in situ, taking advantage of a mutation, ecdysone, which causes an increase in size of these terminals. Using patch-clamp techniques, we have analyzed voltage-dependent potassium currents at the macroscopic and single-channel level. The synaptic membrane contained at least two distinct voltage-activated potassium currents with different kinetics and voltage sensitivity: an IA-like current with fast activation and inactivation kinetics and voltage-dependent steady-state inactivation; a complex delayed current that includes a slowly inactivating component, resembling the IK described in other preparations; and a noninactivating component. The IA-like current in these peptidergic boutons is not encoded by the gene Shaker, because it is not affected by null mutations at this locus. Rather, synaptic IA has properties similar to those of the Shal-encoded IA. Single-channel recordings revealed the presence in synaptic membranes of three different potassium channel types (A2, KD, KL), with biophysical properties that could account for the macroscopic currents and resemble those of the Shal, Shab, and Shaw channels described in heterologous expression systems and Drosophila neuronal somata. A2 channels (6-9 pS) have brief open times, and like the macroscopic IA they exhibited voltage-dependent steady-state inactivation and a rapidly inactivating ensemble average current profile. KD channels (13-16 pS) had longer open times, activate and inactivate with much slower kinetics, and may account for the slowly inactivating component of the macroscopic current. KL (44-54 pS) channels produced a noninactivating ensemble average and may contribute to the delayed macroscopic current observed.

Animals↗

PubMed1994

Molecular biology of the KATP channel. Where's the clone?

Explore the source record for details and available documents.

ATP-Binding Cassette Transporters↗

PubMed2006

Blockers of the delayed-rectifier potassium current in pancreatic beta-cells enhance glucose-dependent insulin secretion.

Delayed-rectifier K+ currents (I(DR)) in pancreatic beta-cells are thought to contribute to action potential repolarization and thereby modulate insulin secretion. The voltage-gated K+ channel, K(V)2.1, is expressed in beta-cells, and the biophysical characteristics of heterologously expressed channels are similar to those of I(DR) in rodent beta-cells. A novel peptidyl inhibitor of K(V)2.1/K(V)2.2 channels, guangxitoxin (GxTX)-1 (half-maximal concentration approximately 1 nmol/l), has been purified, characterized, and used to probe the contribution of these channels to beta-cell physiology. In mouse beta-cells, GxTX-1 inhibits 90% of I(DR) and, as for K(V)2.1, shifts the voltage dependence of channel activation to more depolarized potentials, a characteristic of gating-modifier peptides. GxTX-1 broadens the beta-cell action potential, enhances glucose-stimulated intracellular calcium oscillations, and enhances insulin secretion from mouse pancreatic islets in a glucose-dependent manner. These data point to a mechanism for specific enhancement of glucose-dependent insulin secretion by applying blockers of the beta-cell I(DR), which may provide advantages over currently used therapies for the treatment of type 2 diabetes.

Amino Acid Sequence↗

PubMed1999

Structural and functional characterization of Kv6.2 a new gamma-subunit of voltage-gated potassium channel.

We have cloned and functionally expressed Kv6.2, a new member of the Kv6 subfamily of voltage-gated potassium channel subunits. The human Kv6.2 (KCNF2) gene was mapped at 18q22-18q23. Kv6.2 mRNA is preferentially expressed in rat and human myocard. Rat and human Kv6.2 subunits appear to be unable to form functional Kv channels in a heterologous expression system, but, when coexpressed with Kv2.1 alpha subunits, heteromultimeric Kv channels were formed mediating voltage-activated delayed-rectifier type outward currents. Their kinetics and conductance-voltage relationship were different from those mediated by homomultimeric Kv2.1 channels. Yeast two-hybrid reporter assays indicated that Kv6.2 amino-termini are able to interact specifically with the Kv2.1 amino-terminus. It is proposed that this protein protein interaction underlies Kv2.1/Kv6.2 subunit assembly and the expression of functional heteromultimeric Kv2.1/Kv6.2 channels. The most resiliant feature of the Kv2.1/Kv6.2 channels was their submicromolar sensitivity to the antiarrhythmic drug propafenone. The data suggest that delayed-rectifier type channels containing Kv6.2 subunits may contribute to cardiac action potential repolarization.

Amino Acid Sequence↗

PubMed2001

GYGD pore motifs in neighbouring potassium channel subunits interact to determine ion selectivity.

Cells maintain a negative resting membrane potential through the constitutive activity of background K+ channels. A novel multigene family of such K+ channels has recently been identified. A unique characteristic of these K+ channels is the presence of two homologous, subunit-like domains, each containing a pore-forming region. Sequence co-variations in the GYGD signature motifs of the two pore regions suggested an interaction between neighbouring pore domains. Mutations of the GYGD motif in the rat drk1 (Kv2.1) K+ channel showed that the tyrosine (Y) position was important for K+ selectivity and single channel conductance, whereas the aspartate (D) position was a critical determinant of open state stability. Tandem constructs engineered to mimic the GYGx-GxGD pattern seen in two-domain K+ channels delineated a co-operative intersubunit interaction between the Y and D positions, which determined ion selectivity, conductance and gating. In the bacterial KcsA K+ channel crystal structure, the equivalent aspartate residue (D80) does not directly interact with permeating K+ ions. However, the data presented here show that the D position is able to fine-tune ion selectivity through a functional interaction with the Y position in the neighbouring subunit. These data indicate a physiological basis for the extensive sequence variation seen in the GYGD motifs of two-domain K+ channels. It is suggested that a cell can precisely regulate its resting membrane potential by selectively expressing a complement of two-domain K+ channels.

Amino Acid Motifs↗

PubMed2003

Kv channel subunits that contribute to voltage-gated K+ current in renal vascular smooth muscle.

The rat renal arterial vasculature displays differences in K(+) channel current phenotypes along its length. Small arcuate to cortical radial arteries express a delayed rectifier phenotype, while the predominant Kv current in larger arcuate and interlobar arteries is composed of both transient and sustained components. We sought to determine whether Kvalpha subunits in the rat renal interlobar and arcuate arteries form heterotetramers, which may account for the unique currents, and whether modulatory Kvbeta subunits are present in renal vascular smooth muscle cells. RT-PCR indicated the presence of several different Kvalpha subunit isoform transcripts. Co-immunoprecipitation with immunoblotting and immunohistochemical evidence suggests that a portion of the K(+) current phenotype is a heteromultimer containing delayed-rectifier Kv1.2 and A-type Kv1.4 channel subunits. RT-PCR and immunoblot analyses also demonstrated the presence of both Kvbeta1.2 and Kvbeta1.3 in renal arteries. These results suggest that heteromultimeric formation of Kvalpha subunits and the presence of modulatory Kvbeta subunits are important factors in mediating Kv currents in the renal microvasculature and suggest a potentially critical role for these channel subunits in blood pressure regulation.

Animals↗

PubMed2004

Calnexin regulates mammalian Kv1 channel trafficking.

Voltage-gated Kv1 channels are key factors regulating excitability in the mammalian central nervous system. Diverse posttranslational regulatory mechanisms operate to determine the density, subunit composition, and localization of Kv1 channel complexes in the neuronal plasma membrane. In this study, we investigated the role of the endoplasmic reticulum chaperone calnexin in the intracellular trafficking of Kv1 channels. We found that coexpressing calnexin with the Kv1.2alpha subunit in transfected mammalian COS-1 cells produced a dramatic dose-dependent increase in cell surface Kv1.2 channel complexes. In calnexin-transfected COS-1 cells, the proportion of Kv1.2 channels with mature N-linked oligosaccharide chains was comparable to that observed in neurons. In contrast, calnexin coexpression exerted no effects on trafficking of the intracellularly retained Kv1.1 or Kv1.6alpha subunits. We also found that calnexin and auxiliary Kvbeta2 subunit coexpression was epistatic, suggesting that they share a common pathway for promoting Kv1.2 channel surface expression. These results provide yet another component in the elaborate repertoire of determinants regulating the density of Kv1 channels in the plasma membrane.

Animals↗