Intracellular sodium-calcium dissociation in early contractile failure in hypoxic ferret papillary muscles.

1. Intracellular sodium activity (aNai) and intracellular calcium activity (aCai) were measured in isolated quiescent right-ventricular ferret muscle: aNai = 9.8 +/- 2.2 mM and aCai = 71 +/- 19 nM. 2. When the muscles were exposed to 10(-5) M-ouabain, aNai increased to 20.4 +/- 3.1 mM while aCai increased to 260 +/- 99 nM. Twitch tension approximately doubled. 3. During prolonged hypoxia with glucose in the perfusate, aNai and twitch tension were unchanged. 4. During prolonged hypoxia with sucrose (substrate free) in the perfusate aNai increased to 18.9 +/- 3.1 mM, but aCai did not change. Twitch tension declined by 50%. 5. The addition of 10(-5) M-ouabain to the substrate-free hypoxic perfusate caused aNai to increase to 31.6 +/- 2.8 mM and aCai to increase to 150 +/- 35 nM. Twitch tension was unchanged. 6. These data indicate that only during prolonged substrate-free hypoxia does aNai increase. Despite the increase in aNai, no change in aCai is seen, unless the sodium-potassium pump is concomitantly inhibited. The lack of rise of aCai is consistent with inhibition of the sodium-calcium exchange, although other avenues of calcium exchange cannot be excluded.