Calcium sparklets regulate local and global calcium in murine arterial smooth muscle

In arterial smooth muscle, protein kinase Cα (PKCα) coerces discrete clusters of L‐type Ca 2+ channels to operate in a high open probability mode, resulting in subcellular domains of nearly continual Ca 2+ influx called ‘persistent Ca 2+ sparklets’. Our previous work suggested that steady‐state Ca 2+ entry into arterial myocytes, and thus global [Ca 2+ ] i , is regulated by Ca 2+ influx through clusters of L‐type Ca 2+ channels operating in this persistently active mode in addition to openings of solitary channels functioning in a low‐activity mode. Here, we provide the first direct evidence supporting this ‘Ca 2+ sparklet’ model of Ca 2+ influx at a physiological membrane potential and external Ca 2+ concentration. In support of this model, we found that persistent Ca 2+ sparklets produced local and global elevations in [Ca 2+ ] i . Membrane depolarization increased Ca 2+ influx via low‐activity and high‐activity persistent Ca 2+ sparklets. Our data indicate that Ca 2+ entering arterial smooth muscle through persistent Ca 2+ sparklets accounts for approximately 50% of the total dihydropyridine‐sensitive (i.e. L‐type Ca 2+ channel) Ca 2+ influx at a physiologically relevant membrane potential (−40 mV) and external Ca 2+ concentration (2 m m ). Consistent with this, inhibition of basal PKCα‐dependent persistent Ca 2+ sparklets decreased [Ca 2+ ] i by about 50% in isolated arterial myocytes and intact pressurized arteries. Taken together, these data support the conclusion that in arterial smooth muscle steady‐state Ca 2+ entry and global [Ca 2+ ] i are regulated by low‐activity and PKCα‐dependent high‐activity persistent Ca 2+ sparklets.