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

1 Department and Graduate Institute of Pharmacology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 2 Department of Physiology and Biophysics, University of Calgary, Calgary, Alberta, Canada; and 3 Department of Pharmacology, University of Vermont, Burlington, Vermont Submitte...

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Published in:American journal of physiology. Heart and circulatory physiology 2007-02, Vol.292 (2), p.H1085-H1094
Main Authors: Wu, Bin-Nan, Luykenaar, Kevin D, Brayden, Joseph E, Giles, Wayne R, Corteling, Randolph L, Wiehler, William B, Welsh, Donald G
Format: Article
Language:English
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Summary:1 Department and Graduate Institute of Pharmacology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 2 Department of Physiology and Biophysics, University of Calgary, Calgary, Alberta, Canada; and 3 Department of Pharmacology, University of Vermont, Burlington, Vermont Submitted 25 August 2006 ; accepted in final form 13 October 2006 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 [GenBank] , 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 agonist; and 2 ) inhibited by calphostin C, a PKC inhibitor. These findings suggest that, by modulating PKC, mechanical stimuli can regulate K IR activity and consequently the electrical and mechanical state of intact cerebral arteries. We propose that the mechanoregulation of K IR channels plays a role in the development of myogenic tone. cerebral arteries; potassium channels; vasoconstrictor stimuli Address for reprint requests and other correspondence: D. G. Welsh, Smooth Muscle Research Group, HMRB-G86, Heritage Medical Research Bldg., Univ. of Calgary, 3330 Hospital Dr. NW, Calgary, Alberta, Canada, T2N-4N1 (e-mail: dwelsh{at}ucalgary.ca )
ISSN:0363-6135
1522-1539
DOI:10.1152/ajpheart.00926.2006