FUNCTIONAL-CHANGES IN SODIUM CONDUCTANCES IN THE HUMAN NEUROBLASTOMA CELL-LINE SH-SY5Y DURING IN-VITRO DIFFERENTIATION

1. The electrophysiological properties of voltage-dependent sodium cur rents were studied in the human neuroblastoma cell line SH-SY5Y before and after in vitro differentiation with retinoic acid, with the use o f the whole cell variant of the patch-clamp technique. 2. Voltage step s from a holding level of -90 mV to depolarizing potentials elicited. in both undifferentiated and differentiated cells, fast inward sodium currents that were full inactivating and tetrodotoxin sensitive. 3. In undifferentiated cells the current peaked at -10 mV, the half-activat ion potential was -35 mV. and the half-inactivation potential was -81 mV. In differentiated cells the current peaked at +10 mV, the half-act ivation potential was -28 mV1 and the half-inactivation potential was -56 mV. Moreover, the peak current amplitude was about a factor of 2 l arger and inactivation kinetics was about a factor of 2 slower than in undifferentiated cells. 4. This diversity in sodium channel propertie s was related to differences in cell excitability. Under current-clamp conditions. intracellular injection of rectangular depolarizing curre nt stimuli from a hyperpolarized membrane potential of about -100 mV e licited graded and weak regenerative responses in undifferentiated cel ls, whereas overshooting action potentials with faster rising phases c ould be elicited in differentiated cells.