Biophys J, December 1999, p. 3319-3327, Vol. 77, No. 6

Energetics of Na⁺-Ca²⁺ Exchange in Resting Cardiac Muscle

 ^*Laboratorios de Metabolismo y Energética Cardíaca, Instituto de Investigaciones Cardiológicas, Facultad de Medicina, UBA, CONICET; Cátedra de Biofísica, Facultad de Odontología, UBA, Buenos Aires, Argentina and  ^#Cardiovascular Research Laboratories, Department of Physiology, School of Medicine, UCLA, Los Angeles, California, USA

The energetic effect of extracellular Na⁺ removal and readmission (in a nominally Ca²⁺-free perfusate) in Langendorff-perfused ventricles of transgenic mice (TM), which overexpress the sarcolemmal Na⁺-Ca²⁺ exchanger; normal mice (NM); young (7-12 days old) rats (YR); and older (13-20 days old) rats (OR) was studied. In all heart muscles, extracellular Na⁺ removal induced an increase in heat production (H₁). Na⁺ readmission further increased heat production to a peak value (H₂) followed by a decrease toward initial values. These effects were more marked in the YR and TM as compared with the OR and NM groups, respectively. Caffeine (1 mM), ryanodine (0.2 µM), and verapamil (1 µM) decreased H₁ and H₂ in both rat groups. EGTA (1 mM) decreased H₁ and H₂ in the YR but not in the OR group. Thapsigargin (1 µM) decreased H₁ and H₂ in all four hearts preparations. A possible interpretation is that Na⁺-Ca²⁺ exchange acts as an energy-saving mechanism to prevent Ca²⁺ accumulation at the junctional sarcoplasmic reticulum zone (JSR) and thus prevents further release of Ca²⁺. Extracellular Na⁺ removal lead to Ca²⁺ accumulation in the JSR inducing further SR-Ca²⁺ release and increased energy release. Na⁺ readmission removes the accumulated Ca²⁺ at the JSR (cleft) zone by exchanging Ca²⁺ with Na⁺ producing a transitory increase in energy release due to Na⁺-K pump activation.

Biophys J, December 1999, p. 3319-3327, Vol. 77, No. 6
© 1999 by the Biophysical Society   0006-3495/99/12/3319/09  $2.00