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

The electrophysiological properties of voltage-dependent outward curre nts were investigated under voltage-clamp conditions in the human neur oblastoma cell line SH-SY5Y before and after in vitro differentiation with retinoic acid, by using the whole cell variant of the patch-clamp technique. Voltage steps to depolarizing potentials from a holding le vel of -90 mV elicited, in both undifferentiated and differentiated ce lls, outward potassium currents that were blocked by tetraethylammoniu m, but were unaffected by 4-aminopyridine, cadmium, and by shifts of t he holding potentials to -40 mV. These currents activated rapidly and inactivated slowly in a voltage-dependent manner. In undifferentiated cells the threshold for current activation was about -30 mV, with a st eady-state half activation potential of 19.5 mV, Maximum conductance w as 4.3 nS and mean conductance density was 0.34 mS/cm(2). Steady-state half inactivation potential was -13.8 mV and similar to 10% of the cu rrent was resistant to inactivation. Both activation and inactivation kinetics were voltage dependent. In differentiated cells the threshold for current activation was about -20 mV, with a half potential for st eady-state activation of 37.0 mV. Maximum conductance was 15.2 nS and mean conductance density was 0.78 mS/cm(2). Steady-state half inactiva tion potential was -9.7 mV and similar to 37% of the current was resis tant to inactivation, Both activation and inactivation kinetics were v oltage dependent. This diversity in potassium channel properties obser ved between undifferentiated and differentiated cells was related to d ifferences in cell excitability. Under current-clamp conditions, the a ction potential repolarization rate in differentiated cells was about threefold faster than that of the abortive action potentials elicitabl e in undifferentiated cells. Furthermore, during prolonged stimulation , trains of spikes could be generated in some differentiated cells but not in undifferentiated cells.