CARDIAC NA+/CA2+ EXCHANGER OPERATES AS A VOLTAGE-REGULATED CYTOSOLIC CALCIUM BUFFER

We examined the contribution of Na+/Ca2+ exchanger to the regulation of intracellular Ca2+ concentration ([Ca2+](i)), by recording the Na+/Ca2+ exchange current (I-NaCa) in guinea-pig ventricular myocytes. Our results show the following: 1) voltage-clamp steps activate a transient I-Naca, which involves a shift in its reversal potential (E(NaCa)) toward the membrane potential (V-m) imposed; 2) the shift of E(NaCa) reflects the change in [Ca2+](i) caused through the operation of the exchanger, while the coincidental change in intracellular Na+ concentration ([Na+](i)) does not contribute to the shift; and 3) a transient I-NaCa is also activated on perturbation of [Ca2+](i) by flash photolysis of caged calcium, indicating that the exchanger compensates the perturbed [Ca2+](i) level. We conclude that the cardiac Na+/Ca2+ exchanger operates to maintain [Ca2+](i) at the level that makes E(NaCa) equal to the membrane potential. The exchanger maintains [Ca2+](i) at a low level during diastole (< 66 nM for V-m < -60 mV), and at a high level during systole (> 1.4 mu M for V-m > +20 mV) in physiological conditions.