Modulation of Electrical Activity and of Intracellular Calcium Oscillations of Smooth Muscle Cells by Calcium Antagonists, Agonists, and Vasopressin

The A7r5 smooth muscle cell line, which originally was derived from fetal rat aorta, shows spontaneous calcium oscillations associated with electrical activity (frequency of 0.2–0.5 Hz). Organic calcium antagonists such as isradipine (10 M) stopped the calcium oscillations whereas calcium agonists (e.g., Bay K 8644, 10 M) increased the frequency and amplitude of calcium oscillations without changing the shape of the electrical spikes. The enantiomers of the dihydropyridine SDZ 202–791 known to have opposite activity with respect to L-type Ca channels antagonized each other when tested for their effects on the calcium oscillations. The modulation of the activity of these cells by inorganic ions that affect Ca and K channels was also investigated. The addition of barium chloride (10 M) to the bathing solution increased the spiking rate whereas cadmium chloride (10 M) abolished the spikes. The vasoconstrictor peptide vasopressin first induced a hyperpolarization associated with the cessation of spiking activity followed by a slow depolarization. The intracellular Ca concentration ([Ca]i), measured with the calcium indicator fura-2. was increased transiently to a level about 10-fold above basal and then gained a new steady state at about twice the basal level. Vasopressin stimulated Ca release from intracellular stores (via Ins P3). resulting in membrane hyperpolarization through activation of Ca -activated K channels. The late and long-lasting [Ca]i elevation was due to Ca influx through dihydropyridine-insensitive channels. These results suggest that the initial depolarization phase of the action potential of these smooth muscle cells is predominantly caused by an opening of dihydropyridine-sensitive (L-type) calcium channels whereas initial repolarization and the following hyperpolarization are probably due to activation of Ca -activated K channels.