SEARCH · PubMed Health

Results for “Delayed Rectifier Potassium Channels”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

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

At least 19 recordsLinked to original sources

PubMed2001

Kv2 channels form delayed-rectifier potassium channels in situ.

A non inactivating potassium current known as the delayed rectifier plays a major role in membrane repolarization during an action potential. Whereas several candidate genes exist that code for potassium current, the identities of the molecular isotypes that are responsible in situ for membrane repolarization remain unidentified. We report that Kv2 channels play a major role in action potential repolarization. Kv2 channel elimination resulted in a reduction of the density of noninactivating potassium current and a prolonged impulse duration. In contrast, suppression of noninactivating current carried by Kv1 channels was much less effective in increasing action potential durations. Thus, whereas different potassium channels encode sustained potassium current, their contributions to action potential repolarization vary and require direct examination in situ. Our results indicate that Kv2 subunits function as classic delayed-rectifier channels in vertebrate neurons.

Action Potentials↗

PubMed1990

Sialic acid and the surface charge of delayed rectifier potassium channels.

We used the whole-cell configuration of the patch-clamp technique and cultured ventricular myocytes from 7-day embryonic chicks to test the hypothesis that sialic acid residues (NANA) constitute the negative surface charge associated with delayed rectifier potassium channels. Delayed rectifier current (iK) was elicited at potentials between -40 and +60 mV. The existence of negative fixed charges close to the "gating sensor" was confirmed by a 6.8-mV negative shift of the half-activation potential (V1/2) following a 10-fold reduction of divalent cations and a 22.6-mV position shift following the addition of 10 mM NiCl2. An 8.4-mV increase in the Boltzmann equation slope factor (k) in the former experiment and a 5.5-mV decline in the latter suggested that the surface charge is not uniformly distributed. We used a high performance liquid chromatography procedure to detect freed sarcolemmal NANA and found that 71-88% was released by neuraminidase (0.2-2.0 U/ml) during 1-h treatments. Such treatments had no significant effect upon the amplitudes of iK or V1/2. On the other hand, k was increased significantly by the enzyme (2.0 U/ml), but only when Ca2+ was present. Finally, 1-h pre-treatments with neuraminidase (2.0 U/ml) had no effect on the positive shift of V1/2 induced by Ni2+. We conclude that although sarcolemmal NANA may bind Ca2+, it does not constitute the surface charge of delayed rectifier potassium channels.

Animals↗

PubMed2002

The 25-kDa synaptosome-associated protein (SNAP-25) binds and inhibits delayed rectifier potassium channels in secretory cells.

Delayed-rectifier K(+) channels (K(DR)) are important regulators of membrane excitability in neurons and neuroendocrine cells. Opening of these voltage-dependent K(+) channels results in membrane repolarization, leading to the closure of the Ca(2+) channels and cessation of insulin secretion in neuroendocrine islet beta cells. Using patch clamp techniques, we have demonstrated that the activity of the K(DR) channel subtype, K(V)1.1, identified by its specific blocker dendrodotoxin-K, is inhibited by SNAP-25 in insulinoma HIT-T15 beta cells. A co-precipitation study of rat brain confirmed that SNAP-25 interacts with the K(V)1.1 protein. Cleavage of SNAP-25 by expression of botulinum neurotoxin A in HIT-T15 cells relieved this SNAP-25-mediated inhibition of K(DR). This inhibitory effect of SNAP-25 is mediated by the N terminus of K(V)1.1, likely by direct interactions with K(Valpha)1.1 and/or K(V)beta subunits, as revealed by co-immunoprecipitation performed in the Xenopus oocyte expression system and in vitro binding. Taken together we have concluded that SNAP-25 mediates secretion not only through its participation in the exocytotic SNARE complex but also by regulating membrane potential and calcium entry through its interaction with K(DR) channels.

Animals↗

PubMed1997

Effects of Pb2+ on delayed-rectifier potassium channels in acutely isolated hippocampal neurons.

Effects of Pb2+ on delayed-rectifier potassium channels in acutely isolated hippocampal neurons. J. Neurophysiol. 78: 2649-2654, 1997. The effects of Pb2+ on delayed-rectifier potassium currents were studied in acutely isolated hippocampal neurons (CA1 neurons, CA3 neurons, granule cells) from the guinea pig using the patch-clamp technique in the whole cell configuration. Pb2+ in micromolar concentrations decreased the potassium currents in a voltage-dependent manner, which appeared as a shift of the current-voltage relation to positive potentials. The effect was reversible after washing. The concentration-responsiveness measured in CA1 neurons revealed an IC50 value of 30 mu mol/l at a potential of -30 mV. The half-maximal shift of the current-voltage relation was reached at 33 mu mol/l and the maximal obtainable shift was 13.4 mV. For the different types of hippocampal neurons, the shift of the current-voltage relation was distinct and was 7.9 mV in CA1 neurons, 13.7 mV in CA3 neurons, and 14.2 mV in granule cells with 50 micro mol/l Pb2+. The effects described here of Pb2+ on the potassium currents in hippocampal neurons and the differences between the types of hippocampal neurons correspond with the known properties and distributions of cloned potassium channels found in the hippocampus. As a whole, our results demonstrate that Pb2+ in micromolar concentration is a voltage-dependent, reversible blocker of delayed-rectifier potassium currents of hippocampal neurons. This effect has to be taken into consideration as a possible contributing mechanism for the neurological symptoms of enhanced brain activity seen during Pb2+ intoxication.

4-Aminopyridine↗

PubMed1999

Changes in the mRNA levels of delayed rectifier potassium channels in human atrial fibrillation.

INTRODUCTION: We measured mRNA levels of delayed rectifier potassium channels in human atrial tissue to investigate the mechanism of the shortening of the atrial effective refractory period and the loss of rate-adaptive shortening of the atrial effective refractory period in human atrial fibrillation. METHODS AND RESULTS: A total of 34 patients undergoing open heart surgery were included. Atrial tissue was obtained from the right atrial free wall, right atrial appendage, left atrial free wall and left atrial appendage, respectively. The mRNA amounts of KVLQT1 (IKs), minK (beta-subunit of IKs), HERG (IKr), and KV1.5 (IKur) were measured by reverse transcription-polymerase chain reaction and normalized to the mRNA amount of GAPDH. We found that the mRNA levels of KV1.5, HERG and KVLQT1 were all significantly decreased in patients with persistent atrial fibrillation for more than 3 months. In contrast, the mRNA level of minK was significantly increased in patients with persistent atrial fibrillation for more than 3 months. We further showed that these changes were independent of the underlying cardiac disease, atrial filling pressure, gender and age. We also found that there was no spatial dispersion of mRNA levels among the four atrial sampling sites. CONCLUSIONS: Because the decrease in potassium currents results in a prolonged action potential, the shortening of the atrial effective refractory period in atrial fibrillation should be attributed to other factors. However, the decrease in IKs might contribute, at least in part, to the loss of rate-adaptive shortening of the atrial refractory period.

Adolescent↗

PubMed1989

Rubidium ions and the gating of delayed rectifier potassium channels of frog skeletal muscle.

1. Unitary currents were measured through delayed rectifier potassium channels of frog skeletal muscle, under conditions where either potassium or rubidium ions carried current. 2. Unitary currents were reduced in amplitude when Rb+ was the charge carrier, indicating that Rb+ permeated the channel less readily than did K+. On the other hand permeability ratios (PRb/PK) measured from the change in reversal potential upon ionic substitution were 0.92 for the external and 0.67 for the internal mouth of the channel. 3. Ensemble-averaged currents activated under depolarization along a similarly S-shaped time course whether K+ or Rb+ carried current, though slightly more slowly in Rb+. However, under repolarization to a negative level, tail currents were prolonged about tenfold in Rb+. 4. The duration of channel opening was substantially prolonged in Rb+. The distribution of open times was fitted by a single exponential whether K+ or Rb+ was the charge carrier, indicating a single open state. But the mean open time, averaged over all voltages investigated, was 2.65 times greater in Rb+. 5. The prolongation in Rb+ of tail currents under repolarization was associated with increases in the number of openings per burst and in the number of bursts during each tail. 6. The implications of these results for channel gating are discussed. It is argued that an early step in channel activation is more voltage dependent than later steps.

Action Potentials↗

PubMed2001

[Inhibition of voltage-activated outward delayed rectifier potassium channel currents in dorsal root ganglion neurons of rats by lead].

OBJECTIVE: To study the effect of lead on voltage-activated outward delayed rectifier potassium channel currents in acute isolated dorsal root ganglion (DRG) neurons of adult rats. METHODS: Patch clamp technique was employed to record the whole cell of DRG in adult rats. RESULTS: In the experiments, delayed rectifier (IK) potassium currents channel was recorded and activation was voltage-dependent. The threshold concentration of lead (Pb2+) for IK was 1 mumol/L, which reduced potassium current by (8.6 +/- 0.8)%, 4 mumol/L of Pb2+ reduced the current by (38.6 +/- 6.2)%, and 8 mumol/L of Pb2+ reduced the current by (63.0 +/- 5.1)%. The action of lead was rapid and its effect would be reversed rapidly to various extent by washing. CONCLUSION: Higher outward delayed rectifier potassium channel currents, which could be reversed.

Animals↗

PubMed1986

Adrenergic modulation of the delayed rectifier potassium channel in calf cardiac Purkinje fibers.

We have investigated the modulation of the delayed rectifier potassium channel in calf cardiac Purkinje fibers by the neurohormone norepinephrine. We find that 0.5 microM norepinephrine increases this K channel current by a factor of 2.7. A maximal increase of about four was found for concentrations of 1 microM and above. Norepinephrine produced a small (less than 5 mV) and variable shift of the K channel reversal potential toward more negative values. The kinetics of the potassium channel are well described by a two-exponential process, both in the absence and presence of norepinephrine. However, norepinephrine substantially decreases the slower time constant with no significant effect on the fast time constant. Potassium channel activation curves in the presence of norepinephrine are very similar to control curves except at large positive potentials. A simple sequential three-state model for this channel can reproduce these data both with and without norepinephrine. The logarithms of the rate constants derived from this model are quadratic functions of voltage, suggesting the involvement of electric field-induced dipoles in the gating of this channel. Most of the kinetic effects of norepinephrine appear to be on a single rate constant.

Animals↗

PubMed1995

Bistability in cerebellar Purkinje cell dendrites modelled with high-threshold calcium and delayed-rectifier potassium channels.

Phase-plane analysis of the ionic currents underlying dendritic plateau potentials was carried out to study the nonlinear dynamics and steady-state transfer properties of the dendritic tree in cerebellar Purkinje cells. The results of an analysis of the P-type calcium and delayed rectifier potassium channel system are presented in this study. These channels constitute a simple system that can support bistability and plateau potentials. By requiring both the steady-state current-voltage curve and nullclines to mimic basic plateau potential properties, we obtained well-defined ranges of specific conductance that can support bistability. Hysteresis was found to be surprisingly prevalent in this simple ion-channel system. Using the steady-state current voltage relationship, we derive concise, algebraic expressions for the voltage and current thresholds of state transitions as functions of specific conductance. The significance of bistability in this ion-channel system is discussed with respect to the generation of plateau potentials in Purkinje cells dendrites and the role of the cerebellum in motor control.

Action Potentials↗

PubMed1993

Single delayed rectifier potassium channels from rabbit coronary artery myocytes.

Cell-attached patches from rabbit coronary artery single smooth muscle cells contained two distinct potassium channel types, namely a large conductance calcium-activated potassium channel and a smaller voltage-activated potassium channel representing the delayed rectifier (IK). When a physiological potassium ion gradient was used, the average slope conductance of single IK channels was 7.26 pS. The time course of activation measured from ensemble averages was well fit by a single exponential raised to the power of 2 and was voltage dependent. Experiments were then performed with potassium (140 mM) on both sides of the membrane to resolve single IK channel currents during deactivation. Ensemble averages of this activity were well described by a two-component exponential, and the time constants were voltage dependent. Mean open times were significantly shorter during deactivation than during activation. Closed time distributions typically had two components. These kinetic characteristics were used in testing various state models for voltage-dependent potassium channels.

Animals↗

PubMed1987

The action of external tetraethylammonium ions on unitary delayed rectifier potassium channels of frog skeletal muscle.

1. We have used single-channel recording to investigate the block by extracellular tetraethylammonium ions (TEA+) of delayed rectifier potassium channels of frog skeletal sarcolemma. 2. TEA+ blocks by reducing the apparent amplitude of unitary currents, without detectable increase in open-level current variance. 3. The block by TEA+ appeared to be 1:1, the fractional current being halved at 5.8 mM and -3 mV. The dissociation constant for the block was voltage dependent, increasing e-fold for a 138 mV depolarization. 4. Activation of delayed rectifier potassium currents is not altered by TEA+. 5. Open times, which in the presence of TEA+ represents bursts of open and blocked events, are not increased by TEA+, indicating that blocked channels are able to close normally.

Action Potentials↗

PubMed1998

The small GTP-binding protein RhoA regulates a delayed rectifier potassium channel.

Tyrosine kinases activated by G protein-coupled receptors can phosphorylate and thereby suppress the activity of the delayed rectifier potassium channel Kv1.2. Using a yeast two-hybrid screen, we identified the small GTP-binding protein RhoA as a necessary component in this process. Coimmunoprecipitation experiments confirmed that RhoA associates with Kv1.2. Electrophysiological analyses revealed that overexpression of RhoA markedly reduced the basal current generated by Kv1.2 expressed in Xenopus oocytes. Furthermore, in 293 cells expressing Kv1.2 and ml muscarinic acetylcholine receptors, inactivating RhoA using C3 exoenzyme blocked the ability of ml receptors to suppress Kv1.2 current. Therefore, these results demonstrate that RhoA regulates Kv1.2 activity and is a central component in the mechanism of receptor-mediated tyrosine kinase-dependent suppression of Kv1.2.

ADP Ribose Transferases↗

PubMed1998

[Effects of 17 beta-estradiol on delayed rectifier potassium channels in hippocampal pyramidal neurons of the rat].

In the present study, both cell-attached and inside-out patch-clamp techniques were used to detect the effects of 17 beta-estradiol (E2) on 42 pS delayed rectifier potassium channels in acutely dissociated hippocampal neurons of new-born SD rats. The results indicated that after application of 1.0 and 10.0 nmol/L E2, the open probabilities of K+ channels were decreased from (67.4 +/- 18.2)% to (41.2 +/- 12.5)% and from (56.3 +/- 15.8)% to (13.2 +/- 12.6)% respectively, the open frequencies were reduced from (43.40 +/- 6.7) Hz to (27.68 +/- 9.1) Hz and from (38.19 +/- 10.1) Hz to (15.79 +/- 3.5) Hz respectively. Meanwhile, there was a shortening of the mean open time and a lenghtening of the mean close time of the channels. The above results suggest that E2 has suppressive effects on the activities of the channels, which might be exerted through a direct action on the cellular membrane.

Animals↗

PubMed1997

Identification of the delayed rectifier potassium channel, Kv1.6, in cultured astrocytes.

Astrocytes are an abundant glial cell type of the central nervous system that appear to play a role in regulating extracellular potassium concentrations in brain, thereby contributing to the maintenance of normal neuronal activity. Voltage-gated potassium conductances, shown to be present in astrocytes, may be involved in this and other astrocytic functions. Toward defining the role of voltage-gated potassium channels in astrocytes, total RNA prepared from cultured mouse cortical astrocytes was screened, using a reverse transcriptase-polymerase chain reaction (RT-PCR) approach, for the expression of several members of the Shaker-like potassium channel subfamily (Kv1.1-Kv1.6). A relatively high level of Kv1.6 transcript was identified by RT-PCR and then confirmed and quantitated by ribonuclease protection assays using a Kv1.6-specific riboprobe. Immunocytochemical staining showed double-labeling of glial fibrillary acidic protein-positive cells with antibody specific for the Kv1.6 channel. The Kv1.6 protein expression was variable among the individual astrocytes. Outward voltage-gated currents were studied in astrocytes in primary culture using the Nystatin-perforated patch voltage clamp technique. Outward potassium currents were observed in all cells studied, and this current was partially blocked by perfusion with 100 nM dendrotoxin (DTX) in 14 of 16 cells tested. This DTX-sensitive current appeared to be a sustained outward potassium current, consistent with the suggestion that the Shaker-like potassium channel Kv1.6 underlies a portion of the delayed rectifier potassium current in cultured mouse cortical astrocytes.

Animals↗

PubMed1998

Detection of transcripts for delayed rectifier potassium channels in the Xenopus laevis inner ear.

Reverse transcriptase polymerase chain reaction (RT-PCR) was used to amplify sequences for delayed rectifier potassium (drk) channel transcripts in Xenopus laevis inner ear and brain. We used degenerate primers that spanned a region between the N-terminal cytoplasmic portion and a region located between the S2 and S3 transmembrane domains of the potassium channel protein. When inner ear total RNA or brain mRNA was used as a template for RT-PCR, a unique product of the expected size (approximately 560 bp) was observed as a single band after electrophoresis on agarose gels. The PCR product from reactions using X. laevis genomic DNA as template was similarly sized, indicating a lack of introns in this region. The RT-PCR products from inner ear and brain were isolated, cloned, and sequenced. Sequence analysis showed that the X. laevis inner ear and brain clones were identical. Sequence alignments of the cloned RT-PCR products with posted GenBank sequences established that the drk sequences from X. laevis inner ear and brain share highest identity with larval X. laevis brain, mouse, rat, and human Kv2 sequences. Positive signals were obtained from inner ear and brain mRNA in Northern dot blots hybridized with digoxigenin labeled probes from the inner ear clone. Taken together, results provide evidence for the expression of Kv2 sequences in the X. laevis inner ear and brain.

Amino Acid Sequence↗

PubMed2000

Sensitivity of native and cloned hippocampal delayed-rectifier potassium channels to verapamil.

The effects of the phenylalkylamine verapamil on native and cloned hippocampal voltage-operated potassium channels were investigated. Native channels were studied in acutely isolated CA1 neurons from the guinea pig with the whole-cell patch-clamp technique. Cloned channels were expressed in oocytes of Xenopus laevis and studied with the two-electrode voltage-clamp technique. Native potassium channels: Verapamil suppressed the potassium currents in micro- and submicromolar concentrations. The current suppression increased during the voltage step. The IC50 value of verapamil was 3 micromol/l and the Hill coefficient was 0.5 indicating a mixed population of potassium channels with distinct verapamil sensitivity. Cloned potassium channels: The hippocampal potassium channels Kv1.1, Kv1.2, Kv1.3, Kv2.1, Kv3.1 and Kv3.2 were affected by verapamil in micromolar concentrations. The effect increased with depolarization time, was voltage-dependent, reached 90% of the maximum within around 40 s after start of verapamil application, recovered slowly after wash-out and did not reach control values even after wash-out times of six minutes. The IC50 values differed markedly and were 35 micromol/l for the Kv1.1 channel, 98 micromol/l for the Kv1.2 channel, 12 micromol/l for the Kv1.3 channel, 226 micromol/l for the Kv2.1 channel, 6 micromol/l for the Kv3.1 channel and 11 micromol/l for the Kv3.2 channel.

Animals↗

PubMed1996

Effects of density and gating of delayed-rectifier potassium channels on resting membrane potential and its fluctuations.

The aim of this study is to evaluate directly, using a reduced experimental system, the nature of interactions between voltage-gated potassium channels and the resting membrane potential. Xenopus oocytes were injected with various concentrations of cRNA coding for a delayed-rectifier potassium channel Shaker-IR. The effects of the density and kinetics of the expressed channels on resting membrane potential is explored in isolated ("inside-out") patches. The channel density is given in terms of maximal conductance (Gmax), measured from the maximal slope of the I-V curve under voltage clamp conditions. The capacitance of the experimental setup is approximately 1 pF. At high channel densities (Gmax > 10 pA/mV) the mean membrane potential is stabilized at approximately -60 mV. This resting membrane potential is more than 35 mV positive to the reversal potential for potassium ions under the same experimental conditions. Analyses of voltage clamp experiments indicate that at high channel densities the mean membrane potential is determined by the rates of channel activation and deactivation, but is not affected by the rates involved in the process of slow (C-type) inactivation. In contrast, at lower channel densities membrane potential is very unstable, and its mean value and amplitude of fluctuations are strongly affected by the process of slow (C-type) inactivation.

Animals↗

PubMed1997

IsK and KvLQT1: mutation in either of the two subunits of the slow component of the delayed rectifier potassium channel can cause Jervell and Lange-Nielsen syndrome.

The Jervell and Lange-Nielsen syndrome (JLNS) comprises profound congenital sensorineural deafness associated with syncopal episodes. These are caused by ventricular arrhythmias secondary to abnormal repolarisation, manifested by a prolonged QT interval on the electrocardiogram. Recently, in families with JLNS, Neyroud et al. reported homozygosity for a single mutation in KVLQT1 , a gene which has previously been shown to be mutated in families with dominantly inherited isolated long QT syndrome [Neyroud et al . (1997) Nature Genet ., 15, 186-189]. We have analysed a group of families with JLNS and shown that the majority are consistent with mutation at this locus: five families of differing ethnic backgrounds were homozygous by descent for markers close to the KVLQT1 gene and a further three families from the same geographical region were shown to be homozygous for a common haplotype and to have the same homozygous mutation of the KVLQT1 gene. However, analysis of a single small consanguineous family excluded linkage to the KVLQT1 gene, establishing genetic heterogeneity in JLNS. The affected children in this family were homozygous by descent for markers on chromosome 21, in a region containing the gene IsK . This codes for a transmembrane protein known to associate with KVLQT1 to form the slow component of the delayed rectifier potassium channel. Sequencing of the affected boys showed a homozygous mutation, demonstrating that mutation in the IsK gene may be a rare cause of JLNS and that an indistinguishable phenotype can arise from mutations in either of the two interacting molecules.

Chromosomes, Human, Pair 21↗