cGMP inhibits the activity of single calcium channels in embryonic chick heart cells.
Effects of cGMP on the slow (L-type) Ca2+ channels of cultured chick embryonic cardiomyocytes were investigated by a cell-attached patch-clamp method. Superfusion of the single cells with 8-bromo-cGMP, a membrane-permeable derivative of cGMP, inhibited the single-channel activity. The cyclic nucleotide decreased, in a concentration-dependent manner, the ensemble averaged currents obtained from multichannel patches. 8-Bromo-cGMP (1 mM) completely abolished the currents (n = 8), whereas 0.1 mM only slightly decreased the currents (n = 4). The influence of cGMP on the characteristics of the single Ca2+ channels was examined using 0.3 mM 8-bromo-cGMP. Unit amplitude and slope conductance of the Ca2+ channel was not changed (25 pS in control versus 24 pS in the presence of cGMP). Analysis of single-channel kinetics showed that cGMP prolonged the slow time constant for the closed-time histogram (from 6.7 to 15.4 msec); the other time constants (for the open-time and closed-time histograms) were not affected. cGMP-induced inhibition of the Ca2+ channels may be mediated by cGMP-dependent protein kinase, because 8-bromo-cGMP is a potent activator of this protein kinase and does not stimulate cAMP hydrolysis. The present results suggest that cGMP opposes the effects of cAMP on the L-type Ca2+ channels in myocardial cells.
Tohse
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Department of Physiology and Biophysics, University of Cincinnati, College of Medicine, Ohio 45267-0576.
Sperelakis
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N
D000818:Animals; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D002478:Cells, Cultured; D002642:Chick Embryo; D000242:Cyclic AMP / Q000037:antagonists & inhibitors; D006152:Cyclic GMP / Q000494:pharmacology*; D004594:Electrophysiology; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D012815:Signal Processing, Computer-Assisted
D015220:Calcium Channels; D000242:Cyclic AMP; D006152:Cyclic GMP