Cav1.2 Underlies Calcium Sparklets in Arterial Smooth Muscle

In arterial smooth muscle, activation of PKCα promotes small clusters of L‐type Ca 2+ channels (LTCC) to operate in a high probability mode, creating sites of nearly continual Ca 2+ influx (Ca 2+ sparklets). At present, the molecular identity of the LTCC underlying Ca 2+ sparklet activity remains unclear. We found that tsA‐201 cells expressing LTCC Cav1.2 and Cav1.3 produced Ca 2+ sparklets with similar quantal event amplitude, gating modalities, and PKCα modulation to those observed in arterial myocytes. Ca 2+ sparklets in arterial myocytes and tsA‐201 expressing Cav1.2 were eliminated by nifedipine (10 μM). In contrast, nifedipine (10 μM) did not eliminate Ca 2+ sparklets produced by Cav1.3 in tsA‐201 cells, suggesting that these channels do not underlie Ca 2+ sparklets in arterial myocytes. Accordingly, application of 10 μM nifedipine abrogated Ca 2+ sparklet activity in wild type, but not in arterial myocytes expressing mutant, dihydropyridine‐insensitive Cav1.2. In addition, the biophysical properties of L‐type Ca 2+ currents in arterial myocytes are similar to those produced by Cav1.2, but not Cav1.3 expressed in tsA‐201 cells. Consistent with our electrophysiological and imaging data, we did detect RNA and protein expression for Cav1.2, but not for Cav1.3 in isolated arterial myocytes. Our data indicate that Cav1.3 and Cav1.2 can produce Ca 2+ sparklets. However, these findings demonstrate that Cav1.2 channels underlie Ca 2+ sparklets in arterial myocytes.