NA-CA EXCHANGE AND THE TRIGGER FOR SARCOPLASMIC-RETICULUM CA RELEASE - STUDIES IN ADULT-RABBIT VENTRICULAR MYOCYTES

The importance of Na-Ca exchange as a trigger for sarcoplasmic reticul um (SR) Ca release remains controversial. Therefore, we measured whole -cell Ca currents (I-Ca), Na-Ca exchange currents (I-NaCa), cellular c ontractions, and intracellular Ca transients in adult rabbit cardiac m yocytes, We found that changing pipette Na concentration markedly affe cted the relationship between cell shortening (or Ca transients) and v oltage, but did not affect the Ca current-voltage relationship. We the n inhibited Na-Ca exchange and varied SR content (by changing the numb er of conditioning pulses before each test pulse). Regardless of SR Ca content, the relationship between contraction and voltage was bell-sh aped in the absence of Na-Ca exchange. Next, we rapidly and completely blocked I-Ca by applying nifedipine to cells. Cellular shortening was variably reduced in the presence of nifedipine, The component of shor tening blocked by nifedipine had a bell-shaped relationship with volta ge, whereas the ''nifedipine-insensitive'' component of contraction in creased with voltage. With the SR disabled (ryanodine and thapsigargin pretreatment), I-Ca could initiate late-peaking contractions that wer e similar to 70% of control amplitude. In contrast, nifedipine-insensi tive contractions could not be elicited in the presence of ryanodine a nd thapsigargin. Finally, we recorded reverse Na-Ca exchange currents that were activated by membrane depolarization. The estimated sarcolem mal Ca flux occurring by Na-Ca exchange (during voltage clamp steps to +30 mV) was similar to 10-fold less than that occurring by I-Ca. Ther efore, Na-Ca exchange alone is unlikely to raise cytosolic Ca concentr ation enough to directly activate the myofilaments. We conclude that r everse Na-Ca exchange can trigger SR Ca release. Because of the sigmoi dal relationship between the open probability of the SR Ca release cha nnel and pCa, the effects of I-Ca and I-NaCa may not sum in a linear f ashion. Rather, the two triggers may act synergistically in the modula tion of SR release.