CaV1.2 sparklets in heart and vascular smooth muscle.

CaV1.2 sparklets are local elevations in intracellular Ca(2+) ([Ca(2+)]i) resulting from the opening of a single or small cluster of voltage-gated, dihydropyridine-sensitive CaV1.2 channels. Activation of CaV1.2 sparklets is an early event in the signaling cascade that couples membrane depolarization to contraction (i.e., excitation-contraction coupling) in cardiac and arterial smooth muscle. Here, we review recent work on the molecular and biophysical mechanisms that regulate CaV1.2 sparklet activity in these cells. CaV1.2 sparklet activity is tightly regulated by a cohort of protein kinases and phosphatases that are targeted to specific regions of the sarcolemma by the anchoring protein AKAP150. We discuss a model for the local control of Ca(2+) influx via CaV1.2 channels in which a signaling complex formed by AKAP79/150, protein kinase C, protein kinase A, and calcineurin regulates the activity of individual CaV1.2 channels and also facilitates the coordinated activation of small clusters of these channels. This results in amplification of Ca(2+) influx, which strengthens excitation-contraction coupling in cardiac and vascular smooth muscle.