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 currents were studied in the human neuroblastoma cell line SH-SY5Y before and after in vitro differentiation with retinoic acid, with the use of the whole cell variant of the patch-clamp technique. 2. Voltage steps 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-activation potential was -35 mV, and the half-inactivation potential was -81 mV. In differentiated cells the current peaked at + 10 mV, the half-activation potential was -28 mV, and the half-inactivation potential was -56 mV. Moreover, the peak current amplitude was about a factor of 2 larger and inactivation kinetics was about a factor of 2 slower than in undifferentiated cells. 4. This diversity in sodium channel properties was related to differences in cell excitability. Under current-clamp conditions, intracellular injection of rectangular depolarizing current stimuli from a hyperpolarized membrane potential of about -100 mV elicited graded and weak regenerative responses in undifferentiated cells, whereas overshooting action potentials with faster rising phases could be elicited in differentiated cells.