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Molecular Pharmacology

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Cardiovascular KCNQ (Kv7) Potassium Channels: Physiological Regulators and New Targets for Therapeutic Intervention

Alexander R. Mackie and Kenneth L. Byron
Molecular Pharmacology November 2008, 74 (5) 1171-1179; DOI: https://doi.org/10.1124/mol.108.049825
Alexander R. Mackie
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Abstract

Potassium channels play an important role in electrical signaling of excitable cells such as neurons, cardiac myocytes, and vascular smooth muscle cells (VSMCs). In particular, the KCNQ (Kv7) family of voltage-activated K+ channels functions to stabilize negative resting membrane potentials and thereby opposes electrical excitability. Of the five known members of the mammalian Kv7 family, Kv7.1 was originally recognized for its role in cardiac myocytes, where it contributes to repolarization of the cardiac action potential. Kv7.2 to Kv7.5 were first discovered in neurons, in which they play a well characterized role in neurotransmitter-stimulated action potential firing. Over the past 5 years, important new roles for Kv7 channels have been identified. Kv7 channels have been found to be expressed in VSMCs from several vascular beds where they contribute to the regulation of vascular tone. There is evidence that Kv7.5 channels in VSMCs are targeted by the hormone vasopressin to mediate its physiological vasoconstrictor actions and evidence that neuronal Kv7 channels in the baroreceptors of the aortic arch adjust the sensitivity of the mechanosensitive neurons to changes in arterial blood pressure. These newly identified physiological roles for Kv7 channels in the cardiovascular system warrant increased attention because pharmacological modulators of this family of channels are being used clinically to treat a variety of neurological disorders. This raises questions about the cardiovascular side effects associated with existing therapies, but there is also obvious potential to capitalize on the established and evolving pharmacology of these channels to develop new therapies for cardiovascular diseases.

Footnotes

  • This work was supported by the American Heart Association (0715618Z to A.R.M.).

  • ABBREVIATIONS: ACh, acetylcholine; AD, Alzheimer's disease; AVP, arginine vasopressin; IPA, intrapulmonary artery; MASMC, mesenteric artery smooth muscle cell; PKC, protein kinase C; PVM, portal vein myocyte; PVR, peripheral vascular resistance; SAH, subarachnoid hemorrhage; VM, membrane potential; VSMC, vascular smooth muscle cells; BMS204352, (5-chloro-2-methoxyphenyl)-1,3-dihydro-3-fluoro-6-(trifluoromethyl)-2H-indol-2-one; 4-AP, 4-aminopyridine; XE991, 10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone; (S)-1, (S)-N-[1-(3-morpholin-4-yl-phenyl)-ethyl]-3-phenyl-acrylamide.

    • Received June 19, 2008.
    • Accepted August 5, 2008.
  • The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 74 (5)
Molecular Pharmacology
Vol. 74, Issue 5
1 Nov 2008
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OtherMINIREVIEW

Cardiovascular KCNQ (Kv7) Potassium Channels: Physiological Regulators and New Targets for Therapeutic Intervention

Alexander R. Mackie and Kenneth L. Byron
Molecular Pharmacology November 1, 2008, 74 (5) 1171-1179; DOI: https://doi.org/10.1124/mol.108.049825

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OtherMINIREVIEW

Cardiovascular KCNQ (Kv7) Potassium Channels: Physiological Regulators and New Targets for Therapeutic Intervention

Alexander R. Mackie and Kenneth L. Byron
Molecular Pharmacology November 1, 2008, 74 (5) 1171-1179; DOI: https://doi.org/10.1124/mol.108.049825
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  • Article
    • Abstract
    • Historical Perspective
    • Kv7 Channel Pharmacology
    • Kv7 Channels in Vascular Smooth Muscle Cells
    • Function of Kv7 Channels in the Context of Multiple Kv Channel Subtypes Expressed in Vascular Myocytes
    • Indirect Effects of Kv7 Channel Modulation on the Cardiovascular System
    • Cardiovascular Kv7 Channels as Therapeutic Targets
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