Sarcoplasmic reticulum and Na1/Ca21 exchanger function during early and late relaxation in ventricular myocytes

Yao, Atsushi, Hiroshi Matsui, Kenneth W. Spitzer, John H. B. Bridge, and William H. Barry. Sarcoplasmic reticulum and Na1/Ca21 exchanger function during early and late relaxation in ventricular myocytes. Am. J. Physiol. 273 (Heart Circ. Physiol. 42): H2765–H2773, 1997.—The relative importance of the Na1/Ca21 exchanger in the initial and terminal phases of relaxation and the decline in the [Ca]i transient was investigated in adult rabbit ventricular myocytes loaded with the Ca21 indicator fluo 3. For electrically stimulated contractions, the peak intracellular Ca21 concentration ([Ca]i) was 700 6 87 nM and end-diastolic [Ca]i was 239 6 30 nM (0.25 Hz, 37°C, 1.08 mM extracellular Ca21 concentration; n 5 14). Abrupt inhibition of Na1/Ca21 exchange was produced by removal of extracellular Na1 (KCl substitution) and Ca21 [2 mM Ca21-free ethylene glycol-bis(baminoethyl ether)-N,N,N8,N8-tetraacetic acid] by means of a rapid switcher device (SW). Abrupt exposure to high K1 induced an action potential, although sufficient Ca21 remained adjacent to the sarcolemma to induce a contraction (SW beat) and [Ca]i transient that were identical in amplitude to those induced by electrical stimulation (ES beat). The initial relaxation and decline in the [Ca]i transient was not significantly prolonged by abrupt elimination of the Na1/Ca21 exchanger, but the rate and extent of the terminal phase of the decline in the [Ca]i transient were significantly reduced. The first derivative of [Ca]i with respect to time versus [Ca]i during the decline of the [Ca]i transient attributable to sarcoplasmic reticulum (SR) function was estimated from the average SW transients, and that attributable to Na1/Ca21 exchange was estimated from the difference between SW and ES transients. By this analysis, the Na1/Ca21 exchanger produces 13% of the first half of the decline in [Ca]i and 45% of the second half of the decline. We conclude that abrupt inhibition of forward Na1/Ca21 exchange does not significantly affect the amplitude or the initial rate of decline of the [Ca]i transient and relaxation. However, its contribution to the reduction of [Ca]i becomes apparent late during the [Ca]i transient, when cytosolic [Ca]i has been reduced.