8-Bromo-cyclic GMP inhibits the calcium channel current in embryonic chick ventricular myocytes.
Superfusion with 8-bromo-cyclic GMP or intracellular injection of cyclic GMP inhibits calcium-dependent slow action potentials in embryonic chick or guinea pig ventricular cells, suggesting that cyclic GMP inhibits calcium currents. Recently, cyclic GMP has been shown to reduce cyclic AMP-stimulated calcium currents in voltage-clamped ventricular myocytes. Since earlier results in intact cells had suggested that cyclic GMP might inhibit basal (i.e., unstimulated by cyclic AMP) calcium currents, we directly investigated the effect of 8-bromo-cyclic GMP on basal calcium channel currents (using barium as the charge carrier) in voltage-clamped ventricular myocytes isolated from embryonic chick hearts. Superfusion with 1 mM 8-bromo-cyclic GMP (without prior cyclic AMP elevation) progressively decreased peak calcium channel currents (-68% at 15 min after the onset of drug exposure). In contrast, the currents were unchanged during 15 min superfusion with control solution, or 1 mM 8-bromo-GMP (the noncyclic inactive analog of 8-bromo-cyclic GMP). The present results in voltage-clamped embryonic chick heart cells indicate that cyclic GMP can inhibit basal calcium channel currents, apparently through a cyclic AMP-independent mechanism.
Wahler
G M
GM
Department of Physiology and Biophysics, University of Cincinnati College of Medicine, OH 45267-0576.
Rusch
N J
NJ
Sperelakis
N
N
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology*; D000818:Animals; D002121:Calcium Channel Blockers; D002642:Chick Embryo; D004558:Electric Stimulation; D006321:Heart / Q000187:drug effects / Q000196:embryology; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*
D002121:Calcium Channel Blockers; D015124:8-Bromo Cyclic Adenosine Monophosphate