Vanadate inhibits uncoupled Ca efflux but not Na–Ca exchange in squid axons

Abstract

Nerve cells can maintain a very low intracellular calcium concentration ([Ca²⁺]_i) against large Ca²⁺ electrochemical gradients (see ref. 1 for review). The properties of the calcium efflux from these cells depend on [Ca²⁺]_i (ref. 2), and within the physiological range, most Ca efflux depends on ATP (which stimulates with high affinity) and is insensitive to Na_i, Na₀ and Ca₀ (uncoupled Ca efflux). When the [Ca²⁺]_i is well above the physiological range, Ca efflux becomes only partially dependent on ATP (acting now with low affinity), is inhibited by Na_i and is stimulated by Na₀ and Ca₀ (Na–Ca exchange). Orthovanadate, a powerful inhibitor of the (Na⁺+K⁺) ATPase and the Na pump^3,4, also inhibits the Ca-stimulated ATPase activity, which is the enzymatic basis for the uncoupled Ca pump, in human red cells⁵. The experiments reported here show that in squid axons the ATP-dependent uncoupled Ca efflux can be fully and reversibly inhibited by vanadate, whereas concentrations of vanadate 10 times higher have no effect on the Na–Ca exchange. This is another indication that the uncoupled Ca efflux represents an ATP-driven Ca pump, and supports the suggestion that the uncoupled Ca efflux and Na–Ca exchange are mediated by different mechanisms².