Monovalent cation (MC) current in cardiac and smooth muscle cells: regulation by intracellular Mg2+ and inhibition by polycations

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Abstract
Previously we have described a monovalent cation (MC) current that could be unmasked by the removal of extracellular divalent cations in vascular smooth muscle cells (SMC) and cardiac myocytes, but specific and potent inhibitors of MC current have not been found, and the mechanism of its intracellular regulation remains obscure. Here we show that small MC current is present in intact cells and could be dramatically up‐regulated during cell dialysis. MC current in dialyzed cells strongly resembled monovalent cation current attributed to Ca2+ release‐activated Ca2+‐selective (CRAC) channels, but its activation did not require depletion of Ca2+ stores, and was observed when the cells were dialyzed with, or without BAPTA. Intracellular free Mg2+ inhibits MC current with Kd=250 μM. Extracellular (but not intracellular) spermine effectively blocked MC current with Kd =3–10 μM, while store‐operated cations (SOC) channels and capacitative Ca2+ influx were not affected. Spermine effectively inhibited MC current‐induced SMC depolarization, and prevented Ca2+ paradox‐induced vascular contracture. Both, MC and SOC currents were inhibited by 2‐aminoethoxydiphenyl borate (2‐APB). It is concluded that MC current could be regulated by intracellular Mg2+, and low concentrations of extracellular spermine could be used to discriminate it from SOC current, and to assess its role in cellular function. British Journal of Pharmacology (2003) 138, 234–244. doi:10.1038/sj.bjp.0705074

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