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(Circulation Research. 1998;83:1104-1114.)
© 1998 American Heart Association, Inc.

Original Contributions

Ontogeny of Local Sarcoplasmic Reticulum Ca²⁺ Signals in Cerebral Arteries

Ca²⁺ Sparks as Elementary Physiological Events

Maik Gollasch, George C. Wellman, Harm J. Knot, Jonathan H. Jaggar, Deborah H. Damon, Adrian D. Bonev, , Mark T. Nelson

From the Department of Pharmacology, University of Vermont, Burlington.

Correspondence to Mark T. Nelson, Department of Pharmacology, University of Vermont, Burlington, VT 05405. E-mail nelson{at}salus.med.uvm.edu

Abstract—Ca²⁺ release through ryanodine receptors (RyRs) in the sarcoplasmic reticulum is a key element of excitation-contraction coupling in muscle. In arterial smooth muscle, Ca²⁺ release through RyRs activates Ca²⁺-sensitive K⁺ (K_Ca) channels to oppose vasoconstriction. Local Ca²⁺ transients ("Ca²⁺ sparks"), apparently caused by opening of clustered RyRs, have been observed in smooth and striated muscle. We explored the fundamental issue of whether RyRs generate Ca²⁺ sparks to regulate arterial smooth muscle tone by examining the function of RyRs during ontogeny of arteries in the brain. In the present study, Ca²⁺ sparks were measured using the fluorescent Ca²⁺ indicator fluo-3 combined with laser scanning confocal microscopy. Diameter and arterial wall [Ca²⁺] measurements obtained from isolated pressurized arteries were also used in this study to provide functional insights. Neonatal arteries (<1 day postnatal), although still proliferative, have the molecular components for excitation-contraction coupling, including functional voltage-dependent Ca²⁺ channels, RyRs, and K_Ca channels and also constrict to elevations in intravascular pressure. Despite having functional RyRs, Ca²⁺ spark frequency in intact neonatal arteries was 1/100 of adult arteries. In marked contrast to adult arteries, neonatal arteries did not respond to inhibitors of RyRs and K_Ca channels. These results support the hypothesis that RyRs organize during postnatal development to cause Ca²⁺ sparks, and RyRs must generate Ca²⁺ sparks to regulate the function of the intact tissue.

Key Words: Ca²⁺ spark • ryanodine receptor • K⁺ channel • vascular smooth muscle • development

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