A constraint on possible stoichiometries of myocardial sodium-calcium exchange

We have examined the sodium-calcium exchange stoichiometry in Langendorff-perfused rabbit hearts using gamma-emitting tracers under conditions of sodium pump inhibition. Following a 60-min perfusion with 10(-5) acetylstrophanthidin, and extracellular concentrations [Na]o = 70 mM and [Ca]o = 300 microM, intracellular sodium rose to 59.2 mM. At this point an increase in extracellular calcium [Ca]o = 1.52 mM) caused a net efflux of sodium, but an increase in sodium [Na]o = 105 mM) caused no measurable change. When sodium and calcium were simultaneously increased according to the ratio [Na]o)n/[Ca]o = [Na]'o)n/[Ca]'o, a sodium efflux is observed when n = 4, but not when n = 3. These results are consistent with an exchange stoichiometry of 3 Na+ for each Ca2+ ion, but not values of 4 or more.