Membrane properties of a human neuroblastoma II: Effects of differentiation

The SK-N-SH cell line is a human neuroblastoma which when grown under standard culture conditions remains relatively undifferentiated. The undifferentiated SK-N-SH cells are relatively inexcitable: they show only partial active responses to injections of current pulses and lack the depolarizing component of the action potential generating mechanism [Kuramoto et al, 1977]. In this study we report on the membrane properties of two subclones of the SK-N-SH, the SK-N-SH-IN (referred to as IN) and the SK-N-SH-Sy5Y (referred to as 5Y) which exhibit extensive morphological differentiation when grown with 1mM dibutyryl cAMP. Fully differentiated IN and 5Y cells have higher resting membrane potentials, in the range of -50 to -80 mV, and higher input resistance and time constants than do the undifferentiated SK-N-SH parental cell line. After 1 week in culture the differentiated IN and 5Y cells exhibit spike potentials in response to injection of current to the cell body. The presence of the Na2+-dependent depolarization was verified directly by the use of tetrodotoxin (TTX) and indirectly in experiments where veratridine (0.1 mM) markedly enhanced the influx of 22Na+. Taken together, the data indicate that generation of action potentials in these human neuroblastoma cells is to a large extent a function of morphological differentiation.