Cyclic nucleotides depress action potentials in cultured aortic smooth muscle cells.
The effects of cyclic nucleotide analogs and related agents on the Ca2+ 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 microM) and forskolin (1-10 microM) 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 microM) had little effect. Synthetic atrial natriuretic factor (0.01-0.1 microM) 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.
Ousterhout
J M
JM
Department of Physiology and Biophysics, University of Cincinnati, College of Medicine, Ohio 45267-0576.
Sperelakis
N
N
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology / Q000378:metabolism; D009320:Atrial Natriuretic Factor / Q000494:pharmacology; D003994:Bucladesine / Q000494:pharmacology; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology*; D006152:Cyclic GMP / Q000494:pharmacology*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
D013757:Tetraethylammonium Compounds; D009599:Nitroprusside; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D003994:Bucladesine; D009320:Atrial Natriuretic Factor; D000242:Cyclic AMP; D006152:Cyclic GMP; D007545:Isoproterenol