Hyposmotic Challenge Inhibits Inward Rectifying K+ Channels in Cerebral Arterial Smooth Muscle Cells.
From: Department and Graduate Institute of Pharmacology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
American journal of physiology. Heart and circulatory physiology
- Publish Date: Feb 2007
- ISSN: 0363-6135
- Volume: 292
- Issue: 2
- Pages: H1085-94
- Medium: Print
- Language: English
- Citation (JAMA): Wu Bin-Nan, Luykenaar Kevin D, Brayden Joseph E, et al. Hyposmotic Challenge Inhibits Inward Rectifying K+ Channels in Cerebral Arterial Smooth Muscle Cells.. Am. J. Physiol. Heart Circ. Physiol. Feb 2007;292:H1085-94
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 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.
Mesh Headings (Keywords): 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid, Animals, Cerebral Arteries, Female, Hypotonic Solutions, Membrane Potentials, Muscle, Smooth, Vascular, Myocytes, Smooth Muscle, Naphthalenes, Patch-Clamp Techniques, Potassium Channels, Inwardly Rectifying, Protein Kinase C, Protein Kinase Inhibitors, RNA, Messenger, Rats, Rats, Sprague-Dawley, Serotonin, Tetradecanoylphorbol Acetate, Uridine Triphosphate, Vasoconstrictor Agents
Check for Full Text / PubMed Unique Identifier (PMID): 17056667
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