Cardioprotective drugs decrease the Na+ background current.
Cardiac dysfunctions such as myocardial functional failure and ventricular arrhythmia have been largely attributed to intracellular Ca2+ overload. One of the mechanisms of intracellular Ca2+ overload involves a rapid influx of Ca2+ via Na(+)-Ca2+ exchange during the reperfusion which utilizes the accumulation of Na+ in myocytes during ischemic cardiac arrest. Possible sources of the intracellular Na+ accumulation include Na+ channel, Na(+)-H+ exchange, Na(+)-Ca2+ exchange, and Na+ background current. In this study, we studied the role of the Na+ background current in intracellular Na+ accumulation during the cardiac arrest by measuring the Na+ background current in guinea pig ventricular myocytes with whole cell clamp method and evaluating the effects of cardioprotective drugs on the Na+ background current. The results were as follows: (1) The Na+ background inward current at -40 mV membrane potential was larger at Ca2+ free solution than 1.8 mM Ca2+ solution. (2) The Na+ background current was not affected by verapamil. (3) 2 microM O-(N, N-hexamethylene)-amiloride (HMA) decreased the Na+ background current at negative membrane potential. (4) The new cardioprotective drug, R 56865, decreased the Na+ background current. These results suggest that the Na+ background current plays a role in increasing the intracellular Na+ activity during high K+ cardioplegia and the blocking effect of myoprotective drugs, such as R 56865, on the Na+ background current may contribute to myocardial protection after cardioplegia.
Park
S R
SR
Department of Physiology, Inha University College of Medicine, Inchon, Korea.
Ryu
G H
GH
Suh
C K
CK
D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D052160:Benzothiazoles; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006324:Heart Arrest, Induced; D009206:Myocardium / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism*; D013844:Thiazoles / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D052160:Benzothiazoles; D010880:Piperidines; D013844:Thiazoles; D000584:Amiloride; C054551:R 56865; D012964:Sodium; D014700:Verapamil; D011188:Potassium