Takeda Y, Nystoriak MA, Nieves-Cintron M, Santana LF, Navedo MF. Relationship between Ca2+ sparklets and sarcoplasmic reticulum Ca2+ load and release in rat cerebral arterial smooth muscle. Am J Physiol Heart Circ Physiol 301: H2285-H2294, 2011. First published October 7, 2011; doi:10.1152/ajpheart.00488.2011.-Ca+ sparklets are subcellular Ca2+ signals produced by the opening of sarcolemmal L-type Ca2+ channels. Ca2+ sparklet activity varies within the sarcolemma of arterial myocytes. In this study, we examined the relationship between Ca2+ sparklet activity and sarcoplasmic reticulum (SR) Ca2+ accumulation and release in cerebral arterial myocytes. Our data indicate that the SR is a vast organelle with multiple regions near the sarcolemma of these cells. Ca2+ sparklet sites were located at or <0.2 mu m from SR-sarcolemmal junctions. We found that while Ca2+ sparklets increase the rate of SR Ca2+ refilling in arterial myocytes, their activity did not induce regional variations in SR Ca2+ content or Ca2+ spark activity. In arterial myocytes, L-type Ca2+ channel activity was independent of SR Ca2+ load. This ruled out a potential feedback mechanism whereby SR Ca2+ load regulates the activity of these channels. Together, our data suggest a model in which Ca2+ sparklets contribute Ca2+ influx into a cytosolic Ca2+ pool from which sarco(endo) plasmic reticulum Ca2+-ATPase pumps Ca2+ into the SR, indirectly regulating SR function.