HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 294/3/H1183    most recent 01148.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Park, K. M. Articles by Bolotina, V. M. Search for Related Content PubMed PubMed Citation Articles by Park, K. M. Articles by Bolotina, V. M.

Role of iPLA₂ and store-operated channels in agonist-induced Ca²⁺ influx and constriction in cerebral, mesenteric, and carotid arteries

¹Ion Channel and Calcium Signaling Unit and ²Vascular Biology Unit, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts

Submitted 3 October 2007 ; accepted in final form 19 December 2007

Store-operated channels (SOC) and store-operated Ca²⁺ entry are known to play a major role in agonist-induced constriction of smooth muscle cells (SMC) in conduit vessels. In microvessels the role of SOC remains uncertain, in as much as voltage-gated L-type Ca²⁺ (Ca_L²⁺) channels are thought to be fully responsible for agonist-induced Ca²⁺ influx and vasoconstriction. We present evidence that SOC and their activation via a Ca²⁺-independent phospholipase A₂ (iPLA₂)-mediated pathway play a crucial role in agonist-induced constriction of cerebral, mesenteric, and carotid arteries. Intracellular Ca²⁺ in SMC and intraluminal diameter were measured simultaneously in intact pressurized vessels in vitro. We demonstrated that 1) Ca²⁺ and contractile responses to phenylephrine (PE) in cerebral and carotid arteries were equally abolished by nimodipine (a Ca_L²⁺ inhibitor) and 2-aminoethyl diphenylborinate (an inhibitor of SOC), suggesting that SOC and Ca_L²⁺ channels may be involved in agonist-induced constriction of cerebral arteries, and 2) functional inhibition of iPLA₂β totally inhibited PE-induced Ca²⁺ influx and constriction in cerebral, mesenteric, and carotid arteries, whereas K⁺-induced Ca²⁺ influx and vasoconstriction mediated by Ca_L²⁺ channels were not affected. Thus iPLA₂-dependent activation of SOC is crucial for agonist-induced Ca²⁺ influx and vasoconstriction in cerebral, mesenteric, and carotid arteries. We propose that, on PE-induced depletion of Ca²⁺ stores, nonselective SOC are activated via an iPLA₂-dependent pathway and may produce a depolarization of SMC, which could trigger a secondary activation of Ca_L²⁺ channels and lead to Ca²⁺ entry and vasoconstriction.

store-operated calcium entry; smooth muscle cells; constriction

This article has been cited by other articles:

				S. N. Saleh, A. P. Albert, C. M. Peppiatt-Wildman, and W. A. Large Diverse properties of store-operated TRPC channels activated by protein kinase C in vascular myocytes J. Physiol., May 15, 2008; 586(10): 2463 - 2476. [Abstract] [Full Text] [PDF]