Effects of 8-bromo-cyclic GMP on slow channel mediated action potentials of 3-days-old embryonic chick ventricle.
The role of cyclic GMP in modulation of cardiac slow channel activity was investigated by observing the effects of 8-bromo-cyclic GMP (8-Br-cGMP) on action potentials of isolated ventricle of 3-days-old chick embryo, which exhibit upstroke primarily due to slow channels. 8-Br-cGMP (0.5 & 1 mM) reduced the maximum diastolic potential, maximal upstroke velocity (+Vmax) and overshoot in 30-60 min. 8-Bromo-cyclic AMP (8 Br-cAMP, 0.5 & 1 mM), isoproterenol (Iso, 0.5-5 microM) and forskolin (0.5-2 microM) caused an increase in +Vmax and overshoot. 8-Br-cGMP antagonised this enhancement of +Vmax. Increase in +Vmax and overshoot by Bay-K-8644 (1 microM) was also blocked by 8-Br-cGMP. These findings show that 8-Br-cGMP inhibited the early embryonic cardiac slow channel activity, which contributes significantly to the upstroke of action potential, under basal conditions as well as after its accentuation by elevation of cyclic AMP levels (by 8-Br-cAMP, Iso & Forskolin) or by direct stimulation of the channel activity (by Bay-K-8644). It is suggested on the basis of these findings that cyclic GMP plays a key role in down modulation of the cardiac slow channel activity in early embryonic chick heart.
Tripathi
O
O
Department of Physiology and Biophysics, College of Medicine, University of Cincinnati, Ohio 45267-0576.
Sperelakis
N
N
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000037:antagonists & inhibitors*; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002642:Chick Embryo; D005576:Colforsin / Q000494:pharmacology; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000494:pharmacology; D006352:Heart Ventricles / Q000196:embryology*; D007473:Ion Channels / Q000502:physiology; D007545:Isoproterenol / Q000494:pharmacology; D016276:Ventricular Function / Q000187:drug effects*
D007473:Ion Channels; D005576:Colforsin; C016276:8-bromocyclic GMP; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D006152:Cyclic GMP; D007545:Isoproterenol