In squid nerves intracellular Mg(2+) promotes deactivation of the ATP-upregulated Na(+)/Ca(2+) exchanger.
We investigated the role of intracellular Mg(2+) (Mg(i)(2+)) on the ATP regulation of Na(+)/Ca(2+) exchanger in squid axons and bovine heart. In squid axons and nerve vesicles, the ATP-upregulated exchanger remains activated after removal of cytoplasmic Mg(2+), even in the absence of ATP. Rapid and complete deactivation of the ATP-stimulated exchange occurs upon readmission of Mg(i)(2+). At constant ATP concentration, the effect of intracellular Mg(2+) concentration ([Mg(2+)](i)) on the ATP regulation of exchanger is biphasic: activation at low [Mg(2+)](i), followed by deactivation as [Mg(2+)](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)P(2)] measured in nerve membrane vesicles. Incorporation of PtdIns(4,5)P(2) into membrane vesicles activates Na(+)/Ca(2+) 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) Mg(i)(2+) 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(+)/Ca(2+) exchanger is different in mammalian heart and squid nerves.
DiPolo
R
R
Laboratorio de Permeabilidad Iónica, Centro de Biofísica y Bioquímica, Instituto Venezolano de Investigaciones Cientificas, Caracas 1020-A, Venezuela. rdipolo@ivic.ve
Berberián
G
G
Beaugé
L
L
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000469:Alkaline Phosphatase / Q000494:pharmacology; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001369:Axons / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D049832:Decapodiformes / Q000502:physiology*; D007425:Intracellular Membranes / Q000378:metabolism*; D007474:Ion Exchange; D008274:Magnesium / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism; D009420:Nervous System / Q000378:metabolism*; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000276:immunology; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D010716:Phosphatidylinositols / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000378:metabolism*; D010738:Type C Phospholipases / Q000494:pharmacology; D015854:Up-Regulation
D000906:Antibodies; D019269:Phosphatidylinositol 4,5-Diphosphate; D010716:Phosphatidylinositols; D019831:Sodium-Calcium Exchanger; D000255:Adenosine Triphosphate; D000469:Alkaline Phosphatase; D010738:Type C Phospholipases; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D008274:Magnesium; D002118:Calcium