MODULATION OF SINGLE CARDIAC NA+ CHANNELS BY CYTOSOLIC MG++ IONS

Elementary Na+ currents were recorded in inside-out patches excised from cultured neonatal rat heart myocytes in order to study the influence of cytosolic Mg++ and other bivalent cations present at the cytoplasmic membrane surface on cardiac Na+ channel gating. Exposing the cytoplasmic membrane surface to a Mg++-free environment shortened the open state of cardiac Na+ channels significantly. Tau(open) declined to 62 +/- 2% of the value obtained at 5 mmol/l Mg(i)++. Other channel properties including the tendency to reopen and the elementary current size either changed insignificantly within a 10% range or remained completely unchanged. An almost identical change of tau(open) can be caused by switching from a Mn++ (5 mmol/l) containing internal solution to a Mn++-free internal solution. But tau(open) failed to significantly respond to a variation in internal Ni++ from 5 mmol/l to 0 mmol/l. The same response to internal Mg++ withdrawal was obtained with (-)-DPI-modified, non-inactivating Na+ channels, indicating that the exit rate from the open state remains as sensitive to cytosolic Mg++ variations as in normal Na+ channels with operating inactivation.