LTRPC7 is a Mg center dot ATP-regulated divalent cation channel required for cell viability

The molecular mechanisms that regulate basal or background entry of divalen t cations into mammalian cells are poorly understood. Here we describe the cloning and functional characterization of a Ca2+ - and Mg2+-permeable diva lent cation channel, LTRPC7 (nomenclature compatible with that proposed in ref. 1), a new member of the LTRPC family of putative ion channels. Targete d deletion of LTRPC7 in DT-40 B cells was lethal, indicating that LTRPC7 ha s a fundamental and nonredundant role in cellular physiology. Electrophysio logical analysis of HEK-293 cells overexpressing recombinant LTRPC7 showed large currents regulated by millimolar levels of intracellular Mg.ATP and M g.GTP with the permeation properties of a voltage-independent divalent cati on influx pathway. Analysis of several cultured cell types demonstrated sma ll magnesium-nucleotide-regulated metal ion currents (MagNuM) with regulati on and permeation properties essentially identical to the large currents ob served in cells expressing recombinant LTRPC7. Our data indicate that LTRPC 7, by virtue of its sensitivity to physiological Mg.ATP levels, may be invo lved in a fundamental process that adjusts plasma membrane divalent cation fluxes according to the metabolic state of the cell.