Triggering of sarcoplasmic reticulum Ca release and contraction by reverse mode Na /Ca exchange in trout atrial myocytes

Hove-Madsen, Leif, Anna Llach, Glen F. Tibbits, and Lluis Tort. Triggering of sarcoplasmic reticulum Ca2 release and contraction by reverse mode Na /Ca2 exchange in trout atrial myocytes. Am J Physiol Regul Integr Comp Physiol 284: R1330–R1339, 2003. First published January 16, 2003; 10.1152/ajpregu.00404.2002.—Whole cell patch clamp and intracellular Ca2 transients in trout atrial cardiomyocytes were used to quantify calcium release from the sarcoplasmic reticulum (SR) and examine its dependency on the Ca2 trigger source. Short depolarization pulses (2–20 ms) elicited large caffeine-sensitive tail currents. The Ca2 carried by the caffeine-sensitive tail current after a 2-ms depolarization was 0.56 amol Ca2 /pF, giving an SR Ca2 release rate of 279 amol Ca2 pF 1 s 1 or 4.3 mM/s. Depolarizing cells for 10 ms to different membrane potentials resulted in a local maximum of SR Ca2 release, intracellular Ca2 transient, and cell shortening at 10 mV. Although 100 M CdCl2 abolished this local maximum, it had no effect on SR Ca2 release elicited by a depolarization to 110 or 150 mV, and the SR Ca2 release was proportional to the membrane potential in the range 50 to 150 mV with 100 M CdCl2. Increasing the intracellular Na concentration ([Na ]) from 10 to 16 mM enhanced SR Ca2 release but reduced cell shortening at all membrane potentials examined. In the absence of TTX, SR Ca2 release was potentiated with 16 mM but not 10 mM pipette [Na ]. Comparison of the total sarcolemmal Ca2 entry and the Ca2 released from the SR gave a gain factor of 18.6 7.7. Nifedipine (Nif) at 10 M inhibited L-type Ca2 current (ICa) and reduced the time integral of the tail current by 61%. The gain of the Nif-sensitive SR Ca2 release was 16.0 4.7. A 2-ms depolarization still elicited a contraction in the presence of Nif that was abolished by addition of 10 mM NiCl2. The gain of the Nifinsensitive but NiCl2-sensitive SR Ca2 release was 14.8 7.1. Thus both reverse-mode Na /Ca2 exchange (NCX) and ICa can elicit Ca2 release from the SR, but ICa is more efficient than reverse-mode NCX in activating contraction. This difference may be due to extrusion of a larger fraction of the Ca2 released from the SR by reverse-mode NCX rather than a smaller gain for NCX-induced Ca2 release.