Emergence of a spermine-sensitive, non-inactivating conductance in mature hippocampal CA1 pyramidal neurons upon reduction of extracellular Ca2+: dependence on intracellular Mg2+ and ATP

Large and protracted elevations of intracellular Ca(2+)] and Na(+)] play a crucial role in neuronal injury in ischemic conditions. In addition to excessive glutamate receptor activation, other ion channels may contribute to disruption of intracellular ionic homeostasis. During episodes of ischemia, extracellular Ca(2+)] falls significantly. Here we report the emergence of an inward current in hippocampal CA1 pyramidal neurons in acute brain slices from adult mice upon reduction/removal of Ca(2+)](e). The magnitude of the current was 100-300pA at -65mV holding potential, depending on intracellular constituents. The current was accompanied by intense neuronal discharge, observed in both whole-cell and cell-attached patch configurations. Sustained currents and increased neuronal firing rates were both reversed by restoration of physiological levels of Ca(2+)](e), or by application of spermine (1mM). The amplitudes of the sustained currents were strongly reduced by raising intracellular Mg(2+)], but not by extracellular Mg(2+)] increases. Elevated intracellular ATP also reduced the current. This conductance is similar in several respects to the "calcium-sensing, non-selective cation current" (csNSC), previously described in cultured mouse hippocampal neurons of embryonic origin. The dependence on intracellular ATP] and Mg(2+)] shown here, suggests a possible role for this current in disruption of ionic homeostasis during metabolic stress that accompanies excessive neuronal stimulation.