Ontogeny of Local Sarcoplasmic Reticulum Ca Signals in Cerebral Arteries Ca Sparks as Elementary Physiological Events

Ca release through ryanodine receptors (RyRs) in the sarcoplasmic reticulum is a key element of excitation-contraction coupling in muscle. In arterial smooth muscle, Ca release through RyRs activates Ca-sensitive K (KCa) channels to oppose vasoconstriction. Local Ca 21 transients (“Ca 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 Ca sparks to regulate arterial smooth muscle tone by examining the function of RyRs during ontogeny of arteries in the brain. In the present study, Ca sparks were measured using the fluorescent Ca indicator fluo-3 combined with laser scanning confocal microscopy. Diameter and arterial wall [Ca] 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 Ca channels, RyRs, and KCa channels and also constrict to elevations in intravascular pressure. Despite having functional RyRs, Ca 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 KCa channels. These results support the hypothesis that RyRs organize during postnatal development to cause Ca sparks, and RyRs must generate Ca sparks to regulate the function of the intact tissue. (Circ Res. 1998;83:1104-1114.)