Development of a neural phenotype in differentiating ganglion cell‐derived human neuroblastoma cells

Human neuroblastoma cells (clone SHSY‐5Y) induced to differentiate by 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA) are shown to possess properties characteristic of mature ganglion cells. Elevation of the external K + concentration, exposure to Ca 2+ ionophore A23187, and acetylcholine all stimulate the release of preloaded 3 H‐noradrenaline in the presence but not in the absence of added Ca 2+ . Acetylcholine causes a fall in the 86 Rb + or 14 C‐TPMP equilibrium potential across the plasma membrane and stimulates 86 Rb + efflux. These responses are prevented by atropine. Acetylcholine and muscarine but not nicotine stimulate an increase in 45 Ca 2+ influx, an effect blocked by atropine. None of these responses have been observed in nondifferentiating cells. Muscarinic receptors, however, as measured by the binding of tritiated quinuclidinyl benzilate ( 3 H‐QNB), were present to a similar extent in control and differentiated cells. Both cell types also exhibit an accelerated release of Ca 2+ in response to acetylcholine, but the control cells were at least 1 order of magnitude more sensitive to the agonist.