Sodium-pump injury and arrhythmogenic transient depolarizations in catecholamine-induced cardiac hypertrophy.
The pathogenesis of arrhythmogenic transient depolarizations (TDs) was studied by means of electrophysiological and cytochemical methods in normal and hypertrophied left ventricular myocardium of the rat. In hypertrophy induced by administration of 5 mg/kg isoprenaline once daily for 7 days, the myocardial membrane was depolarized, the action potential duration was prolonged and the Vmax was decreased, as compared with those of age-matched normal controls. TDs induced by a train of action potentials could be observed in hypertrophied myocardium, but not in normal control myocardium. Ryanodine completely abolished TDs, but the beta-adrenoceptor agonist noradrenaline and the adenylate cyclase activator forskolin were without effect. In cytochemical studies, the Na+,K(+)-ATPase activity was localized in the sarcolemma, and three times as much reaction product, which appeared on the inner side of the cell membrane, was found in the normal myocardium than in the hypertrophied myocardium. The results suggest that catecholamine-induced cardiac hypertrophy damages the membrane-bound Na+,K(+)-ATPase and causes a cAMP-independent intracellular Ca overload and TDs, thereby permitting abnormal impulse formation, which predisposes the diseased myocardium to develop arrhythmias.
Mészáros
J
J
Department of Anatomy, Medical University of Debrecen, Hungary.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D006332:Cardiomegaly / Q000139:chemically induced / Q000503:physiopathology*; D005576:Colforsin / Q000494:pharmacology; D004558:Electric Stimulation; D006321:Heart / Q000502:physiology*; D007545:Isoproterenol / Q000633:toxicity*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012433:Ryanodine / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects* / Q000378:metabolism
D012433:Ryanodine; D005576:Colforsin; D000254:Sodium-Potassium-Exchanging ATPase; D007545:Isoproterenol