This Article Full Text Full Text (PDF) 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 PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Knot, H. J. Search for Related Content PubMed PubMed Citation Articles by Knot, H. J.

(Circulation Research. 2001;89:941.)
© 2001 American Heart Association, Inc.

Editorials

Calcium Sparks Unleashed in Vascular Smooth Muscle

Lessons From the RyR3 Knockout Mouse

Harm J. Knot

From the Department of Pharmacology and Therapeutics, University of Florida, and the McKnight Brain Institute, Gainesville, Fla.

Correspondence to Harm J. Knot, University of Florida, Department of Pharmacology, Box 100267, Gainesville, FL 32610. E-mail hknot@college.med.ufl.edu

Key Words: calcium • sparks • cerebral arteries • ryanodine receptors • calcium channels

Hypertension is a progressive disease involving an increase in arterial constriction. It constitutes a major risk factor leading to stroke, heart disease, and kidney failure. Understanding the molecular pathways involved in arterial tone regulation is crucial to increasing our understanding of blood pressure regulation. Recently, a novel mechanism involving small-localized bursts of calcium inside vascular smooth muscle cells, termed Ca²⁺ sparks, was identified that acts as a negative feedback mechanism that opposes vasoconstriction.¹

Ca²⁺ Sparks in Muscle

Ca²⁺ sparks are thought to be the elementary functional Ca²⁺ release signals in heart, skeletal, and smooth muscle cells.^1–4 Ca²⁺ sparks are but one example of the increasing complexity in Ca²⁺ signaling in the spatial and temporal domain in a variety of tissues including arterial smooth muscle.⁵ Ca²⁺ sparks result from the opening of several or the coordinated opening of many, tightly clustered ryanodine receptor Ca²⁺ release channels (RyRs) in the sarcoplasmic reticulum (SR) of muscle cells.^6,7 In arterial smooth muscle and intact arteries, Ca²⁺ sparks are observed just under the cell membrane consistent with a predominant subsarcolemmal localization of the RyR Ca²⁺ release channels in the sarcoplasmic reticulum.^3,8

Function, Distribution, and Localization of RyR Isoforms

The mammalian RyRs are encoded by 3 different genes (RYR1, RYR2, and RYR3). Initial DNA cloning studies in mammalian tissues have assigned the names RyR1 to the subtype dominantly expressed in skeletal muscle, RyR2 to the one in cardiac muscle and RyR3 in brain tissue, respectively.^9,10 The functional properties of RyR1 and RyR2 are well studied because of their dominant expression and role in . . . [Full Text of this Article]

This article has been cited by other articles:

				M. Aoyama, A. Yamada, J. Wang, S. Ohya, S. Furuzono, T. Goto, S. Hotta, Y. Ito, T. Matsubara, K. Shimokata, et al. Requirement of ryanodine receptors for pacemaker Ca2+ activity in ICC and HEK293 cells J. Cell Sci., June 1, 2004; 117(13): 2813 - 2825. [Abstract] [Full Text] [PDF]