Effects of intracellular adenosine-5'-diphosphate and orthophosphate on the sensitivity of sodium efflux from squid axon to external sodium and potassium.

A study was made of sodium efflux from squid giant axon, and its sensitivity to external K and Na. When sodium efflux from untreated axons was strongly stimulated by K(o), Na(o) was inhibitory; when dependence on K(o) was low, Na(o) had a stimulatory effect. Incipient CN poisoning or apyrase injection, which produces high intracellular levels of ADP(1) and P(i), rendered sodium efflux less dependent on external K and more dependent on external Na. Injection of ADP, AMP, arginine, or creatine + creatine phosphokinase, all of which raise ADP levels without raising P(i) levels, had the same effect as incipient CN poisoning. P(i) injection had no effect on the K sensitivity of sodium efflux. Axons depleted of arginine and phosphoarginine by injection of arginase still lost their K sensitivity when the ATP:ADP ratio was lowered and regained it partially when the ratio was raised. Rough calculations show that sodium efflux is maximally K(o)-dependent when the ATP:ADP ratio is about 10:1, becomes insensitive to K(o) when the ratio is about 1:2, and is inhibited by K(o) when the ratio is about 1:10. Deoxy-ATP mimicked ADP when injected into intact axons. Excess Mg, as well as P(i), inhibited both strophanthidin-sensitive and strophanthidin-insensitive sodium efflux. An outline is presented for a model which might explain the effects of ADP, P(i) and deoxy-ATP.