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: 295/3/C779    most recent 00173.2008v1 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 ISI Web of Science (1) Google Scholar Articles by Berra-Romani, R. Articles by Golovina, V. A. PubMed PubMed Citation Articles by Berra-Romani, R. Articles by Golovina, V. A.

VASCULAR BIOLOGY

Ca²⁺ handling is altered when arterial myocytes progress from a contractile to a proliferative phenotype in culture

Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland

Submitted 25 March 2008 ; accepted in final form 25 June 2008

Phenotypic modulation of vascular myocytes is important for vascular development and adaptation. A characteristic feature of this process is alteration in intracellular Ca²⁺ handling, which is not completely understood. We studied mechanisms involved in functional changes of inositol 1,4,5-trisphosphate (IP₃)- and ryanodine (Ry)-sensitive Ca²⁺ stores, store-operated Ca²⁺ entry (SOCE), and receptor-operated Ca²⁺ entry (ROCE) associated with arterial myocyte modulation from a contractile to a proliferative phenotype in culture. Proliferating, cultured myocytes from rat mesenteric artery have elevated resting cytosolic Ca²⁺ levels and increased IP₃-sensitive Ca²⁺ store content. ATP- and cyclopiazonic acid [CPA; a sarco(endo)plasmic reticulum Ca²⁺-ATPase (SERCA) inhibitor]-induced Ca²⁺ transients in Ca²⁺-free medium are significantly larger in proliferating arterial smooth muscle cells (ASMCs) than in freshly dissociated myocytes, whereas caffeine (Caf)-induced Ca²⁺ release is much smaller. Moreover, the Caf/Ry-sensitive store gradually loses sensitivity to Caf activation during cell culture. These changes can be explained by increased expression of all three IP₃ receptors and a switch from Ry receptor type II to type III expression during proliferation. SOCE, activated by depletion of the IP₃/CPA-sensitive store, is greatly increased in proliferating ASMCs. Augmented SOCE and ROCE (activated by the diacylglycerol analog 1-oleoyl-2-acetyl-sn-glycerol) in proliferating myocytes can be attributed to upregulated expression of, respectively, transient receptor potential proteins TRPC1/4/5 and TRPC3/6. Moreover, stromal interacting molecule 1 (STIM1) and Orai proteins are upregulated in proliferating cells. Increased expression of IP₃ receptors, SERCA2b, TRPCs, Orai(s), and STIM1 in proliferating ASMCs suggests that these proteins play a critical role in an altered Ca²⁺ handling that occurs during vascular growth and remodeling.

store-operated calcium entry; receptor-operated calcium entry; canonical transient receptor potential proteins; stromal interaction molecule 1 and Orai proteins