Characteristics of Na(+)‐Ca2+ exchange in frog skeletal muscle.

1. Fluxes studies were carried out to investigate the Na(+)‐dependent outward movement of Ca2+ in intact frog sartorius muscle from Leptodactylus ocellatus, a preparation for which published data on the subject are sparse. 2. Under normal resting conditions the Na(+)‐Ca2+ exchange was not readily detectable. 3. When muscles were exposed to 4 mM caffeine, the rate of fractional loss of Ca2+ (kCa,o) increased by about 50%. Most of this increase exhibits characteristics typical of the Na(+)‐Ca2+ antiport working in the forward mode found in other cells. 4. The increase in kCa,o promoted by caffeine was decreased by: (a) 72% in the absence of external Na+ (Nao+); (b) 73% in Na(+)‐loaded muscles ([Na+]i = 98 mM); (c) 70% when fibres were depolarized to ‐27 mV ([K+]o = 50 mM); and (d) 80% in the presence of 5 mM amiloride. 5. Ni2+ (5 mM), an inhibitor of the Na(+)‐Ca2+ exchanger current, unexpectedly increased the caffeine‐promoted rise in kCa,o. This effect of Ni2+ was associated with a concomitant caffeine‐stimulated Ni2+ influx. In the absence of caffeine Ni2+ did not affect kCa,o. 6. It was concluded that: (a) under resting conditions the sarcolemmal Ca2+ pump suffices to handle the cytosolic calcium concentration ([Ca2+]i); (b) Na(+)‐Ca2+ activity becomes apparent when [Ca2+]i is substantially increased by caffeine‐induced Ca2+ release from the sarcoplasmic reticulum; and (c) the blocking effect of Ni2+ on the current generated by a Na(+)‐Ca2+ exchange with a coupling ratio > 2 might actually represent a shift of the antiport mode toward an electroneutral 1 Ni(2+)‐1Ca2+ exchange.