Dihydropyridine-sensitive Ca²⁺ influx modulated by stretch in A7r5 vascular smooth muscle cells

We examined ⁴⁵Ca²⁺ influx in A7r5 vascular smooth muscle cells under cyclical stretch and static conditions and compared the results obtained at resting membrane potential (2.5 mM [K⁺]_o, E_m = -58 mV according to uptake of [³H]tetraphenylphosphonium) with those under depolarizing conditions (70 mM [K⁺]_o, E_m = -27 mV). Application of 10% average strain (24% maximum) in cycles of 3 s on, 3 s off at resting Em caused a 5-fold increase in Ca²⁺ influx rate to a level similar to depolarized cells and depolarized, stretched cells. 1 μM (+)-isradipine blocked 90% of the stretch-or depolarization-activated Ca²⁺ uptake. When the cells were stretched under Na⁺-free conditions, a reduction, not activation, of Ca²⁺ influx rate occurred. Our results suggest that stretching of cultured aortic vascular smooth muscle cells enhances Ca²⁺ uptake through a voltage-dependent, dihydropyridine-sensitive Ca²⁺ entry pathway, whose activation by stretch is dependent upon extracellular Na⁺.