Energetic effects of caffeine in face of retarded Na+/Ca2+ exchange in isolated, arrested guinea pig hearts.
The effects of caffeine, a widely used pharmacological tool for releasing Ca2+ from the sarcoplasmic reticulum (SR), on the resting rate of oxygen consumption and left ventricular diastolic pressure development of isolated, KCl-arrested, guinea pig hearts was examined. Caffeine (10 mmol/l) had no effect on either the rate of oxygen consumption or left ventricular pressure development. However, when Ca2+ extrusion via the Na+/Ca2+ exchanger was retarded, whether by reducing the external Na+ concentration ([Na+]o) from 143 to 57 mmol/l or through further depolarizing the membrane by increasing external K+ concentration ([K+]o) from 20 to 40 mmol/l, the subsequent introduction of caffeine evoked a pronounced increase in the rate of oxygen consumption. This was accompanied by a small contracture in the low [Na+]o condition only. In the absence of external Ca2+ the stimulatory effects of caffeine on cardiac energetics in either the low [Na+]o or 40 mmol/l [K+]o condition was totally prevented. It is concluded that Na+/Ca2+ exchange plays a major role in dictating the energetic response of the cardiac cell to pharmacological activation of the SR Ca2+ release channel by caffeine.
Department of Physiology, School of Medicine, University of Auckland, New Zealand.
P J
PJ
Hanley
P J
PJ
Cooper
D S
DS
Loiselle
D000704:Analysis of Variance; D000818:Animals; D002110:Caffeine / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D004734:Energy Metabolism / Q000187:drug effects*; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D006323:Heart Arrest / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D010477:Perfusion; D011189:Potassium Chloride / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism*; D016277:Ventricular Function, Left / Q000187:drug effects
D002110:Caffeine; D011189:Potassium Chloride; D012964:Sodium; D002118:Calcium