Ca2+ channel Ca(2+)-dependent inactivation in a mammalian central neuron involves the cytoskeleton

Abstract

Ca2+ channel inactivation was investigated in acutely isolated hippocampal pyramidal neurons from adult rats and found to have a component dependent on intracellular Ca2+. Ca(2+)-dependent inactivation was indentified as the additional inactivation of channel current observed when Ca2+ replaced Ba2+ as the current carrying ion, and was found to be an independent process from that of Ba2+ current inactivation based on three lines of evidence: (1) no correlation between Ca(2+)-dependent inactivation and Ba2+ current inactivation was found, (2) only Ca(2+)-dependent inactivation was reduced by intracellular application of Ca2+ chelators, and (3) only Ca(2+)-dependent inactivation was sensitive to compounds which alter the cytoskeleton. Drugs which stabilize (taxol and phalloidin) and destabilize (colchicine and cytochalasin B) the cytoskeleton altered the development and recovery from Ca(2+)-dependent inactivation, indicating that the neuronal cytoskeleton may mediate Ca2+ channel sensitivity to intracellular Ca2+. Ca(2+)-dependent inactivation was not associated with a particular subset of Ca2+ channels, suggesting that all Ca2+ channels in these neurons are inactivated by intracellular Ca2+.