Intracellular Mg²⁺ can regulate the electrogenic Na⁺-HCO₃⁻ cotransporter activity

Abstract

The electrogenic Na⁺-HCO₃⁻ cotransporter (NBCe) plays a critical role in secretion and absorption of HCO₃⁻ and regulation of intracellular pH in various tissues, and thus its activity is necessary to be regulated tightly. Despite intensive studies, the regulatory mechanisms of NBCe activity have not been fully understood. It has been shown that intracellular Mg²⁺ (Mg²⁺_i) regulates various ion channels and transporters in several ways. In this presentation, we show using the standard whole-cell patch clamp technique that Mg²⁺_i can control natively and heterologously expressed NBCe currents. Mg²⁺_i concentration was varied by pipette solutions having different calculated free Mg²⁺. Native NBCe currents recorded from freshly dissociated bovine parotid acinar cells were inhibited by increasing Mg²⁺_i in a dose-dependent manner (K_i =–1 mM). The native currents were also inhibited by intracellular polyvalent cationic compounds such as neomycin and spermine. Mg²⁺_i and neomycin inhibited heterologous NBCe currents in mammalian cultured cells transiently transfected with the cloned bovine parotid NBCe1-B. These results suggest that Mg²⁺_i might regulate the NBCe1-B activity under physiological conditions, and the underlying mechanism will be discussed. [J Physiol Sci. 2008;58 Suppl:S210]