Cloning and characterization of a Kv1.5 delayed rectifier K+ channel from vascular and visceral smooth muscles

Overturf, Ken; Russell, S. N.; Carl, A.; Vogalis, Fivos; Hart, P. M.; Hume, Joseph R.; Sanders, Kenton M.; Horowitz, Burton

doi:10.1152/ajpcell.1994.267.5.c1231

Cited by 122 publications

(91 citation statements)

References 24 publications

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“…Thus almost 20% of the outward current appears to be non-inactivating. The nature of this component has not been investigated further in this study, but it could reflect a non-inactivating component of IK(V), such as has recently been described by Overturf et al (1994) in colonic circular smooth muscle.…”

Section: Ll7mpsmentioning

confidence: 94%

The pharmacological properties of K⁺ currents from rabbit isolated aortic smooth muscle cells

Halliday

Aaronson

Evans

et al. 1995

British J Pharmacology

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1 Using the whole-cell patch-clamp technique, the effects of several K+ channel blocking drugs on K+ current recorded from rabbit isolated aortic smooth muscle cells were investigated. 2 Upon depolarization from -80 mV, outward K+ current composed of several distinct components were observed: a transient, 4-aminopyridine (4-AP)-sensitive component (Ij) and a sustained component (I,.), comprising a 4-AP-sensitive delayed rectifier current (IKM), and a noisy current which was sensitive to tetraethylammonium (TEA), and probably due to Ca2"-activated K+ current (IK(Ca))-3 Several drugs in clinical or experimental use have as part of their action an inhibitory effect on specific K+ channels. Because of their differential K+ channel blocking effects, these drugs were used in an attempt to characterize further the K+ channels in rabbit aortic smooth muscle cells. Imipramine, phencycidine, sotalol and amitriptyline failed to block selectively any of the components of K+ current, and were thus of little value in isolating individual channel contributions. Clofilium showed selective block of IK(V) in the presence of TEA, but only at low stimulation frequencies (0.07 Hz). At higher frequencies (1 Hz) of depolarization, both It and IK(V) were suppressed to a similar extent. Thus, the blocking action of clofilium was use-dependent.4 The voltage-dependent inactivation of It and the delayed rectifier were very similar although a brief (100 ms) pre-pulse to -30 mV could preferentially inactivate It. Together with the non-selective blocking effects of the K+ channel blockers, similarities in the activation and inactivation of these two components suggest that they may not exist as separate ionic channels, but as distinct kinetic states within the same K+ channel population. 5The effects of all of these drugs on tension were examined in strips of rabbit aorta. The non-specific K+ channel blockers caused only minor increases in basal tension. TEA and 4-AP by themselves caused significant increases in tension and were even more effective when applied together. There appeared to be no correlation between the effects of the drugs tested on tension and their actions on currents recorded from isolated myocytes. Thus tension studies are an inappropriate means of investigating the mechanism of action of these drugs, and studies on ionic currents in isolated myocytes cannot easily predict drug actions on intact tissues.

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Section: Ll7mpsmentioning

confidence: 94%

The pharmacological properties of K⁺ currents from rabbit isolated aortic smooth muscle cells

Halliday

Aaronson

Evans

et al. 1995

British J Pharmacology

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“…Only two members of the Kv3 family (Kv3.1 and Kv3.2) show comparable slowly activating, slowly inactivating currents, but both are exquisitely sensitive to submillimolar TEA (IC 50 = 0.15 to 0.2 mmol/L) (Coetzee et al, 1999). Similarly, the pharmacological profile of Kv1.5 cloned from dog vascular smooth muscle argues against its presence in dog basilar artery (IC 50 = 200 and 365 mmol/L for 4-AP and quinine, respectively, Kv1.5 not blocked by TEA, antagonized by correolide, see Table 1, Figures 2 and 3 for comparison) (Overturf et al, 1994;Albarwani et al, 2003).…”

Section: Identity Of Kv Channels In Dog Basilar Arterymentioning

confidence: 95%

Voltage-Gated K⁺ Channel Dysfunction in Myocytes from a Dog Model of Subarachnoid Hemorrhage

Jahromi

Aihara

et al. 2007

J Cereb Blood Flow Metab

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Delayed cerebral vasospasm after subarachnoid hemorrhage is primarily due to sustained contraction of arterial smooth muscle cells. Its pathogenesis remains unclear. The degree of arterial constriction is regulated by membrane potential that in turn is determined predominately by K+ conductance (GK). Here, we identified the main voltage-gated K+ (Kv) channels contributing to outward delayed rectifier currents in dog basilar artery smooth muscle as Kv2 class through a combination of electrophysiological and pharmacological methods. Kv2 current density was nearly halved in vasospastic myocytes after subarachnoid hemorrhage (SAH) in dogs, and Kv2.1 and Kv2.2 were downregulated in vasospastic myocytes when examined by quantitative mRNA, Western blotting, and immunohistochemistry. Vasospastic myocytes were depolarized and had a smaller contribution of GK toward maintenance of their membrane potential. Pharmacological block of Kv current in control myocytes mimicked the depolarization observed in vasospastic arteries. The degree of membrane depolarization was found to be compatible with the amount of vasoconstriction observed after SAH. We conclude that Kv2 dysfunction after SAH contributes to the pathogenesis of delayed cerebral vasospasm. This may confer a novel target for treatment of delayed cerebral vasospasm.

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“…Defects in members of this class of channels are thus linked to a wide range of cardiovascular diseases (4)(5)(6). The Shaker family of Kv channels has been extensively characterized both functionally and structurally (7,8), and within this group Kv1.5 is widely represented in the cardiovascular system (9). In the human heart Kv1.5 is selectively expressed in atrial myocytes and mediates the ultrarapid K ϩ current (I Kur ) central to action potential repolarization (10).…”

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confidence: 99%

SUMO modification regulates inactivation of the voltage-gated potassium channel Kv1.5

Benson

Kieckhafer

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

134

113

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The voltage-gated potassium (Kv) channel Kv1.5 mediates the IKur repolarizing current in human atrial myocytes and regulates vascular tone in multiple peripheral vascular beds. Understanding the complex regulation of Kv1.5 function is of substantial interest because it represents a promising pharmacological target for the treatment of atrial fibrillation and hypoxic pulmonary hypertension. Herein we demonstrate that posttranslational modification of Kv1.5 by small ubiquitin-like modifier (SUMO) proteins modulates Kv1.5 function. We have identified two membrane-proximal and highly conserved cytoplasmic sequences in Kv1.5 that conform to established SUMO modification sites in transcription factors. We find that Kv1.5 interacts specifically with the SUMO-conjugating enzyme Ubc9 and is a target for modification by SUMO-1, -2, and -3 in vivo. In addition, purified recombinant Kv1.5 serves as a substrate in a minimal in vitro reconstituted SUMOylation reaction. The SUMO-specific proteases SENP2 and Ulp1 efficiently deconjugate SUMO from Kv1.5 in vivo and in vitro, and disruption of the two identified target motifs results in a loss of the major SUMOconjugated forms of Kv1.5. In whole-cell patch-clamp electrophysiological studies, loss of Kv1.5 SUMOylation, by either disruption of the conjugation sites or expression of the SUMO protease SENP2, leads to a selective Ϸ15-mV hyperpolarizing shift in the voltage dependence of steady-state inactivation. Reversible control of voltage-sensitive channels through SUMOylation constitutes a unique and likely widespread mechanism for adaptive tuning of the electrical excitability of cells.electrical excitability ͉ posttranslational modification ͉ transmembrane protein ͉ ubiquitin-like modifier

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Cloning and characterization of a Kv1.5 delayed rectifier K+ channel from vascular and visceral smooth muscles

Cited by 122 publications

References 24 publications

The pharmacological properties of K⁺ currents from rabbit isolated aortic smooth muscle cells

The pharmacological properties of K⁺ currents from rabbit isolated aortic smooth muscle cells

Voltage-Gated K⁺ Channel Dysfunction in Myocytes from a Dog Model of Subarachnoid Hemorrhage

SUMO modification regulates inactivation of the voltage-gated potassium channel Kv1.5

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Cloning and characterization of a Kv1.5 delayed rectifier K+ channel from vascular and visceral smooth muscles

Cited by 122 publications

References 24 publications

The pharmacological properties of K+ currents from rabbit isolated aortic smooth muscle cells

The pharmacological properties of K+ currents from rabbit isolated aortic smooth muscle cells

Voltage-Gated K+ Channel Dysfunction in Myocytes from a Dog Model of Subarachnoid Hemorrhage

SUMO modification regulates inactivation of the voltage-gated potassium channel Kv1.5

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The pharmacological properties of K⁺ currents from rabbit isolated aortic smooth muscle cells

The pharmacological properties of K⁺ currents from rabbit isolated aortic smooth muscle cells

Voltage-Gated K⁺ Channel Dysfunction in Myocytes from a Dog Model of Subarachnoid Hemorrhage