The influence of calcium on sodium efflux in squid axons.

1. Previous work has shown that the sodium efflux from the axons of Loligo forbesi increases when external sodium is replaced by lithium.2. The increase in efflux in lithium was unaffected by ouabain but was abolished by removal of external calcium; in these respects it differed from the potassium-dependent sodium efflux which was abolished by ouabain but not reduced by removal of external calcium.3. Strontium but not magnesium could replace calcium in activating the ouabain-insensitive sodium efflux; lanthanum had an inhibitory effect.4. Replacing all the external NaCl by choline chloride or dextrose gave a rise in Na efflux which was abolished by ouabain but not by removal of external calcium.5. The rise in Na efflux resulting from partial replacement of NaCl by dextrose or choline chloride consisted of two components one of which was ouabain-insensitive and calcium-dependent and the other was inhibited by ouabain but calcium-insensitive.6. The ouabain-insensitive component of the Na efflux was activated by low concentrations of Na, Li or K but inhibited by high concentrations of Na and to a lesser extent Li. The inhibiting effect of high Na was of the kind expected if these ions displace calcium from an external site.7. The ouabain-insensitive component of the Na efflux was abolished by cyanide, had a Q(10) of 2.7; and was roughly proportional to [Na](i) (2). It was much more variable in magnitude than the ouabain-sensitive, potassium-dependent component of the sodium efflux.8. The calcium influx increased five to fortyfold when external NaCl was replaced by LiCl or dextrose, the increase for Li being larger than the increase for dextrose.9. The calcium influx from Na, Li or dextrose sea water was increased three to tenfold by increasing the internal Na about fourfold.10. The experiments provide evidence for a coupling between an inward movement of calcium and an outward movement of sodium.