Document Detail

Hyposmotic challenge inhibits inward rectifying K+ channels in cerebral arterial smooth muscle cells.
MedLine Citation:
PMID:  17056667     Owner:  NLM     Status:  MEDLINE    
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.
Bin-Nan Wu; Kevin D Luykenaar; Joseph E Brayden; Wayne R Giles; Randolph L Corteling; William B Wiehler; Donald G Welsh
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2006-10-20
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  292     ISSN:  0363-6135     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2007 Feb 
Date Detail:
Created Date:  2007-02-08     Completed Date:  2007-03-20     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H1085-94     Citation Subset:  IM    
Department and Graduate Institute of Pharmacology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
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MeSH Terms
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / pharmacology
Cerebral Arteries / drug effects,  metabolism*
Hypotonic Solutions
Membrane Potentials / drug effects
Muscle, Smooth, Vascular / drug effects,  metabolism*
Myocytes, Smooth Muscle / drug effects,  metabolism*
Naphthalenes / pharmacology
Patch-Clamp Techniques
Potassium Channels, Inwardly Rectifying / drug effects,  metabolism*
Protein Kinase C / metabolism*
Protein Kinase Inhibitors / pharmacology
RNA, Messenger / metabolism
Rats, Sprague-Dawley
Serotonin / pharmacology
Tetradecanoylphorbol Acetate / analogs & derivatives,  pharmacology
Uridine Triphosphate / pharmacology
Vasoconstrictor Agents / pharmacology
Reg. No./Substance:
0/Hypotonic Solutions; 0/Kir2.1 channel; 0/Kir2.2 channel; 0/Naphthalenes; 0/Potassium Channels, Inwardly Rectifying; 0/Protein Kinase Inhibitors; 0/RNA, Messenger; 0/Vasoconstrictor Agents; 121263-19-2/calphostin C; 16561-29-8/Tetradecanoylphorbol Acetate; 50-67-9/Serotonin; 56937-68-9/phorbolol myristate acetate; 63-39-8/Uridine Triphosphate; 76898-47-0/15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; EC Kinase C

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