Removal of intracellular Mg2+ activates cardiac Na+/Ca2+ exchanger

See article by Wei et al. [1] (pages 334–340) in this issue. The Na+/Ca2+ exchanger (NCX) expels Ca2+ from myocytes in exchange for extracellular Na+ and balances Ca2+ influx through L-type Ca2+ channels during cardiac excitation. In this issue of Cardiovascular Research, Wei et al. [1] report that cardiac NCX is regulated by intracellular Mg2+ (Mg2+ i ). Their results suggest some similarities of mammalian cardiac NCX to that of squid nerves (NCX-SQ) [2]. In squid nerve, rapid removal of Mg2+ i produced marked activation of the exchanger. Further removal of ATP did not suppress the activated NCX-SQ, but readmission of Mg2+ i abolished this NCX-SQ stimulation. Phosphatidylinositols, which are known to modulate the activity of cardiac NCX [3], were not involved in the stimulation of NCX-SQ by Mg2+ i removal [2]. In pig ventricular myocytes [1], when Mg2+ i was reduced by cell dialysis with a low Mg2+ internal solution (0.18 mM), whole cell NCX current was augmented regardless of the levels of free Ca2+, ATP and MgATP. These findings are quite comparable to those in squid nerves: removal of ATP in the absence of Mg2+ i kept the NCX-SQ in a highly stimulated state. Among the results by Wei et al. [1], the absence of the effect of ATP on stimulated NCX by … * Tel.: +81-975-865-651; fax: +81-975-496-046