Local regulation of L-type Ca²⁺ channel sparklets in arterial smooth muscle

Abstract

This review addresses the latest advances in our understanding of the regulation of a novel Ca²⁺ signal called L-type Ca²⁺ channel sparklets in arterial smooth muscle. L-type Ca²⁺ channel sparklets are elementary Ca²⁺ influx events produced by the opening of a single or a small cluster of L-type Ca²⁺ channels. These Ca²⁺ signals were first visualized in the vasculature in arterial smooth muscle cells. In these cells, L-type Ca²⁺ channel sparklets display two functionally distinct gating modalities that regulate local and global [Ca²⁺](i). The activity of L-type Ca²⁺ channel sparklets varies regionally within a cell depending on the dynamic activity of a cohort of protein kinases and phosphatases recruited to L-type Ca²⁺ channels in the arterial smooth muscle sarcolemma in a complex coordinated by the scaffolding molecule AKAP150. We also described a mechanism whereby clusters of L-type Ca²⁺ channels gate cooperatively to amplify intracellular Ca²⁺ signals with likely pathological consequences.