An ATP-dependent Na/Mg countertransport is the only mechanism for Mg extrusion in squid axons

The components of magnesium efflux in squid axons have been studied under internal dialysis and voltage clamp conditions. The present report rules out the existence of an ATP-dependent, Na₀- and Mg₀-independent Mg²⁺ efflux (ATP-dependent Mg²⁺ pump) leaving the Mg²⁺---Na⁺ exchange system as the only mechanism for Mg²⁺ extrusion. The main features of the Mg²⁺ efflux are: (1) The efflux is completely dependent on ATP. (2) The efflux can be activated either by external Na⁺ (forward Mg²⁺---Na⁺ exchange) or external Mg²⁺ (Mg²⁺---Mg²⁺ exchange). (3) The mobility of the Mg²⁺ exchanger in the Na₀⁺-loaded form is greater than that in the Mg²⁺-loaded one. (4) In variance with the Na⁺---Ca²⁺ exchange mechanism, Mg²⁺---Mg²⁺ exchange is not activated by external monovalent cations. (5) ATPγS replaces ATP in activating Mg²⁺---Na⁺ exchange suggesting that a phosphorylation/dephosphorylation process regulates this transport mechanism.