Calcium sparklets in arterial smooth muscle

1. Voltage-dependent, L-type Ca2+ channels (LTCC) play an essential role in arterial smooth muscle contraction and, consequently, the regulation of arterial diameter, tissue perfusion and blood pressure. However, the spatial organization of functional LTCC in arterial myocytes is incompletely understood. 2. Total internal reflection fluorescence and swept-field confocal microscopy revealed that the opening of a single or a cluster of LTCC produces local elevations in [Ca2+](i) called Ca2+ sparklets. In arterial myocytes, Ca2+ sparklets are produced by the opening of Cav1.2 channels. 3. The Ca2+ sparklet activity is bimodal. In low activity mode, rare stochastic openings of solitary LTCC produce limited Ca2+ influx ('low activity Ca2+ sparklets'). In contrast, discrete clusters of LTCC associated with protein kinase Ca (PKC alpha) operate in a sustained, high-activity mode resulting in substantial Ca2+ influx ('persistent Ca2+ sparklets'). 4. The Ca2+ sparklet activity varies regionally within a myocyte depending on the relative activities of nearby PKC alpha and opposing protein phosphates 2A and 2B. 5. Low- and high-activity persistent Ca2+ sparklets modulate local and global [Ca2+](i) in arterial smooth muscle, suggesting that this Ca2+ signal may play an important role in the regulation of vascular function.