Hyposmotic challenge inhibits inward rectifying K+ channels in cerebral arterial smooth muscle cells

American Journal of Physiology. Heart and Circulatory Physiology
Bin-Nan WuDonald G Welsh

Abstract

This study sought to define whether inward rectifying K(+) (K(IR)) channels were modulated by vasoactive stimuli known to depolarize and constrict intact cerebral arteries. Using pressure myography and patch-clamp electrophysiology, initial experiments revealed a Ba(2+)-sensitive K(IR) current in cerebral arterial smooth muscle cells that was active over a physiological range of membrane potentials and whose inhibition led to arterial depolarization and constriction. Real-time PCR, Western blot, and immunohistochemical analyses established the expression of both K(IR)2.1 and K(IR)2.2 in cerebral arterial smooth muscle cells. Vasoconstrictor agonists known to depolarize and constrict rat cerebral arteries, including uridine triphosphate, U46619, and 5-HT, had no discernable effect on whole cell K(IR) activity. Control experiments confirmed that vasoconstrictor agonists could inhibit the voltage-dependent delayed rectifier K(+) (K(DR)) current. In contrast to these observations, a hyposmotic challenge that activates mechanosensitive ion channels elicited a rapid and sustained inhibition of the K(IR) but not the K(DR) current. The hyposmotic-induced inhibition of K(IR) was 1) mimicked by phorbol-12-myristate-13-acetate, a PKC agon...Continue Reading

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Citations

Jun 24, 2011·Cardiovascular Research·Lisa ChiltonRodger Loutzenhiser
Sep 1, 2009·American Journal of Physiology. Heart and Circulatory Physiology·Matthew A NystoriakGeorge C Wellman
Oct 30, 2012·American Journal of Physiology. Heart and Circulatory Physiology·Rasha R Abd El-RahmanDonald G Welsh
Jan 24, 2012·American Journal of Physiology. Heart and Circulatory Physiology·Francesco VetriDale A Pelligrino
Feb 17, 2009·American Journal of Physiology. Heart and Circulatory Physiology·Kevin D LuykenaarDonald G Welsh
Jan 8, 2011·Journal of Biomedical Science·I-Shan ChenBin-Nan Wu
Jun 17, 2008·Journal of Smooth Muscle Research = Nihon Heikatsukin Gakkai Kikanshi·Eun A KoWon Sun Park
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Jul 29, 2016·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Maria SanchoDonald G Welsh
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Jan 27, 2019·American Journal of Physiology. Heart and Circulatory Physiology·Maria SanchoDonald G Welsh
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Oct 3, 2017·Annual Review of Pharmacology and Toxicology·Donald G WelshMaria Sancho
Feb 1, 2020·American Journal of Physiology. Heart and Circulatory Physiology·Maria SanchoDonald G Welsh
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