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This Article Full Text Full Text (PDF) All Versions of this Article: 576/3/887    most recent jphysiol.2006.113951v1 Services Email this article to a friend Similar articles in this journal 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 Google Scholar Google Scholar Articles by Rueda, A. Articles by Valdivia, H. H. Search for Related Content PubMed PubMed Citation Articles by Rueda, A. Articles by Valdivia, H. H. Related Collections Cardiovascular

¹ Department of Physiology, University of Wisconsin Medical School, Madison, WI 53711, USA
² Department of Anaesthesiology, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095, USA

Spontaneous, local Ca²⁺ release events or Ca²⁺ sparks by ryanodine receptors (RyRs) are important determinants of vascular tone and arteriolar resistance, but the mechanisms that modulate their properties in smooth muscle are poorly understood. Sorcin, a Ca²⁺-binding protein that associates with cardiac RyRs and quickly stops Ca²⁺ release in the heart, provides a potential mechanism to modulate Ca²⁺ sparks in vascular smooth muscle, but little is known about the functional role of sorcin in this tissue. In this work, we characterized the expression and intracellular location of sorcin in aorta and cerebral artery and gained mechanistic insights into its functional role as a modulator of Ca²⁺ sparks. Sorcin is present in endothelial and smooth muscle cells, as assessed by immunocytochemical and Western blot analyses. Smooth muscle sorcin translocates from cytosolic to membranous compartments in a Ca²⁺-dependent manner and associates with RyRs, as shown by coimmunoprecipitation and immunostaining experiments. Ca²⁺ sparks recorded in saponin-permeabilized vascular myocytes have increased frequency, duration and spatial spread but reduced amplitude with respect to Ca²⁺ sparks in intact cells, suggesting that permeabilization disrupts the normal organization of RyRs and releases diffusible substances that control Ca²⁺ spark properties. Perfusion of 2 µM sorcin onto permeabilized myocytes reduced the amplitude, duration and spatial spread of Ca²⁺ sparks, demonstrating that sorcin effectively regulates Ca²⁺ signalling in vascular smooth muscle. Together with a dense distribution in the perimeter of the cell along a pool of RyRs, these properties make sorcin a viable candidate to modulate vascular tone in smooth muscle.

(Received 22 May 2006; accepted after revision 18 August 2006; first published online 24 August 2006)
Corresponding author H. H. Valdivia: Department of Physiology, University of Wisconsin Medical School, 601 Science Dr Madison, WI 53711, USA. Email: valdivia{at}physiology.wisc.edu

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