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Am J Physiol Cell Physiol 279: C1631-C1639, 2000;
0363-6143/00 $5.00
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Vol. 279, Issue 5, C1631-C1639, November 2000

In squid nerves intracellular Mg2+ promotes deactivation of the ATP-upregulated Na+/Ca2+ exchanger

Reinaldo DiPolo1,2, Graciela Berberián3, and Luis Beaugé2,3

1 Laboratorio de Permeabilidad Iónica, Centro de Biofísica y Bioquímica, Instituto Venezolano de Investigaciones Cientificas, Caracas 1020-A, Venezuela; 3 Laboratorio de Biofísica, Instituto de Investigación Médica M. y M. Ferreyra, Consejo Nacional de Investigaciones Científicas y Técnicas, 5000 Córdoba, Argentina; and 2 Marine Biological Laboratory, Woods Hole, Massachusetts 02543

We investigated the role of intracellular Mg2+ (Mgi2+) on the ATP regulation of Na+/Ca2+ exchanger in squid axons and bovine heart. In squid axons and nerve vesicles, the ATP-upregulated exchanger remains activated after removal of cytoplasmic Mg2+, even in the absence of ATP. Rapid and complete deactivation of the ATP-stimulated exchange occurs upon readmission of Mgi2+. At constant ATP concentration, the effect of intracellular Mg2+ concentration ([Mg2+]i) on the ATP regulation of exchanger is biphasic: activation at low [Mg2+]i, followed by deactivation as [Mg2+]i is increased. No correlation was found between the above results and the levels of phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] measured in nerve membrane vesicles. Incorporation of PtdIns(4,5)P2 into membrane vesicles activates Na+/Ca2+ exchange in mammalian heart but not in squid nerve. Moreover, an exogenous phosphatase prevents MgATP activation in squid nerves but not in mammalian heart. It is concluded that 1) Mgi2+ is an essential cofactor for the deactivation part of ATP regulation of the exchanger and 2) the metabolic pathway of ATP upregulation of the Na+/Ca2+ exchanger is different in mammalian heart and squid nerves.

sodium ion/calcium ion exchange; adenosine 5'-triphosphate; intracellular magnesium ion; phosphorylation-dephosphorylation; phosphoinositides


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