Electrophysiological effects of cyclic GMP on canine cardiac Purkinje fibers.
The effect of cyclic 3'5'-guanosine monophosphate (8-bromo-cGMP) on action potential characteristics was investigated. Standard microelectrode techniques were used to study the effects of 8-bromo-cGMP on canine cardiac Purkinje fibers in vitro. Canine Purkinje fiber tissue preparations were exposed to increasing concentrations of 8-bromo-cGMP (10(-6), 10(-5), 10(-4) M). The action potential duration at 50% (APD50) and 90% (APD90) repolarization, resting membrane potential (RMP), action potential amplitude (APA), rate of rise of phase 0 (Vmax), spontaneous rate (SR), escape time (ET), and effective refractory period (ERP) did not change at these concentrations of 8-bromo-cGMP. The effect of 8-bromo-cGMP on isoproterenol (10(-7) M) treated Purkinje fibers was tested. Predictably, isoproterenol shortened APD and ERP and increased SR. APD or ERP shortening was not affected by 8-bromo-cGMP, but the increase in SR produced by isoproterenol was prevented. Eleven of sixteen Purkinje fiber preparations treated with isoproterenol alone became spontaneously arrhythmic, whereas none of six treated with 8-bromo-cGMP and isoproterenol became arrhythmic (p less than 0.05). Slow-response action potentials elicited by potassium depolarization and catecholamines were abbreviated and eventually abolished by 8-bromo-cGMP. In conclusion, 8-bromo-cGMP has no effect on action potential characteristics in normally polarized canine Purkinje fibers but depressed slow response action potentials. The effects of isoproterenol on SR are antagonized and the production of arrhythmias in this model are prevented by 8-bromo-cGMP.
Mehegan
J P
JP
Muir
W W
WW
Unverferth
D V
DV
Fertel
R H
RH
McGuirk
S M
SM
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D011690:Purkinje Fibers / Q000187:drug effects* / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology
C016276:8-bromocyclic GMP; D013779:Tetrodotoxin; D006152:Cyclic GMP; D007545:Isoproterenol