Transmitter, ion channel and receptor properties of pheochromocytoma (PC12) cells: a model for neurotoxicological studies.

The increased desire to use in vitro techniques in neurotoxicology has resulted in the search for clonal cell lines which may be useful for studying disruption by neurotoxicants of various aspects of neuronal physiology and biochemistry. One such cell line is the PC12 cell, a clonal cell line derived from a pheochromocytoma of the rat adrenal medulla. When cultured under normal conditions, PC12 cells resemble adrenal chromaffin cells in morphology, physiology and biochemistry. However, when cultured in the presence of nerve growth factor (NGF) or several other compounds, PC12 cells differentiate to resemble sympathetic neurons morphologically and functionally. Differentiation and the resultant physiological and biochemical changes are some of the most attractive and useful features of this cell line. PC12 cells release, depending on the conditions, dopamine, norepinephrine and acetylcholine and contain Na, K and Ca channels and other membrane receptors, including receptors coupled to G-proteins. Moreover, the relative proportion of various subtypes of Ca channels changes during differentiation. Thus, PC12 cells provide an excellent model for studying chemical disruption of processes associated with neuronal differentiation, synthesis, storage and release of neurotransmitters, function and regulation of ion channels and interactions of compounds with membrane bound receptors. The ability of PC12 cells to differentiate in response to NGF and other compounds allows for selective expression of certain channels and proteins and for comparisons of responses in undifferentiated and differentiated cells. The prominent neurotoxicant methylmercury causes potent reductions in uptake of 45Ca and binding of ligands associated with various subpopulations of Ca channels in the PC12 cells, as well as currents carried through putative Ca channels.