Cyclic nucleotides depress action potentials in cultured aortic smooth muscle cells

Abstract

The effects of cyclic nucleotide analogs and related agents on the Ca 2+ dependent action potentials of cultured rat aortic smooth muscle cells (reaggregates) were examined. The action potentials were elicited by electrical stimulation in the presence of tetraethylammonium (TEA, 5–15 mM). Superfusion of the aortic cells with analogs of cyclic AMP (dibutyryl or 8-bromo-cyclic AMP, 1 mM), isoproterenol (1–10 μM) and forskolin (1–10 μm) depressed and abolished the TEA-induced action potentials. Abolition of the action potentials by these agents was reversible and was accompanied by some hyperpolarization of the membrane. Superfusion with 8-bromo-cyclic GMP (0.1–1 mM) also depressed or abolished the TEA-induced action potentials, whereas dibutyryl cyclic GMP (1 mM) and sodium nitroprusside (10 μM) had little effect. Synthetic atrial natriuretic factor (0.01–0.1 μM) had inhibitory effects in most experiments. Thus, depression of membrane excitability may be a contributing factor in the relaxation of aortic smooth muscle produced by some agents that increase intracellular levels of cyclic nucleotides.