Electrophysiological effects of cyclic GMP on canine cardiac Purkinje fibers. 1985

J P Mehegan, and W W Muir, and D V Unverferth, and R H Fertel, and S M McGuirk

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.

UI MeSH Term Description Entries
D007545 Isoproterenol Isopropyl analog of EPINEPHRINE; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant. Isoprenaline,Isopropylarterenol,4-(1-Hydroxy-2-((1-methylethyl)amino)ethyl)-1,2-benzenediol,Euspiran,Isadrin,Isadrine,Isopropyl Noradrenaline,Isopropylnoradrenaline,Isopropylnorepinephrine,Isoproterenol Hydrochloride,Isoproterenol Sulfate,Isuprel,Izadrin,Norisodrine,Novodrin,Hydrochloride, Isoproterenol,Noradrenaline, Isopropyl,Sulfate, Isoproterenol
D008297 Male Males
D011690 Purkinje Fibers Modified cardiac muscle fibers composing the terminal portion of the heart conduction system. Purkinje Fiber,Fiber, Purkinje,Fibers, Purkinje
D004285 Dogs The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065) Canis familiaris,Dog
D005260 Female Females
D006152 Cyclic GMP Guanosine cyclic 3',5'-(hydrogen phosphate). A guanine nucleotide containing one phosphate group which is esterified to the sugar moiety in both the 3'- and 5'-positions. It is a cellular regulatory agent and has been described as a second messenger. Its levels increase in response to a variety of hormones, including acetylcholine, insulin, and oxytocin and it has been found to activate specific protein kinases. (From Merck Index, 11th ed) Guanosine Cyclic 3',5'-Monophosphate,Guanosine Cyclic 3,5 Monophosphate,Guanosine Cyclic Monophosphate,Guanosine Cyclic-3',5'-Monophosphate,3',5'-Monophosphate, Guanosine Cyclic,Cyclic 3',5'-Monophosphate, Guanosine,Cyclic Monophosphate, Guanosine,Cyclic-3',5'-Monophosphate, Guanosine,GMP, Cyclic,Guanosine Cyclic 3',5' Monophosphate,Monophosphate, Guanosine Cyclic
D006329 Heart Conduction System An impulse-conducting system composed of modified cardiac muscle, having the power of spontaneous rhythmicity and conduction more highly developed than the rest of the heart. Conduction System, Heart,Conduction Systems, Heart,Heart Conduction Systems,System, Heart Conduction,Systems, Heart Conduction
D000200 Action Potentials Abrupt changes in the membrane potential that sweep along the CELL MEMBRANE of excitable cells in response to excitation stimuli. Spike Potentials,Nerve Impulses,Action Potential,Impulse, Nerve,Impulses, Nerve,Nerve Impulse,Potential, Action,Potential, Spike,Potentials, Action,Potentials, Spike,Spike Potential
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013779 Tetrodotoxin An aminoperhydroquinazoline poison found mainly in the liver and ovaries of fishes in the order TETRAODONTIFORMES, which are eaten. The toxin causes paresthesia and paralysis through interference with neuromuscular conduction. Fugu Toxin,Tarichatoxin,Tetradotoxin,Toxin, Fugu

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