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BACKGROUND AND AIMS: The aim of this work was to find relationships between Zn accumulation and integrity of cholinergic and astroglial cells. METHODS: Exposition of cAMP/RA-differentiated (DC) and nondifferentiated (NC) cells cholinergic SN56 neuroblastoma and astroglial C6 cells to Zn yielded its concentration dependent accumulation. The level of Zn was measured by fluorimetric method with TSQ. RESULTS: After 24 h exposition of SN56 cells to 0.15 mM Zn their death rates were equal to 35 and 50% for NC and DC at cation levels equal to 4.0 and 5.5 nmol/mg protein, respectively. In the same conditions, the death rates of astroglial cells were close to 1–2% only, at intracellular Zn levels of 1.6 and 2.1 nmol/mg protein, respectively. Higher, about 0.25 mM Zn levels were required to evoke death rates of astroglial cells, similar to those seen in neuronal cells. In such conditions Zn levels in astroglia were about 6.4 and 27.0 nmol/mg protein, respectively. In thisstudy we examined the effects of accumulation of Zn in cholinergic neurons and adjacent astrocytes on activity of enzymes involved in energy metabolism. It caused inhibition of PDHC, aconitase and IDH activities. The high susceptibility of cholinergic neurons and a relative high resistance of astrocytes induced by cytotoxic concentration of zinc. Higher levels of Zn may cause deeper inhibition of acetyl-CoAsynthesis and the flow rate of the TCAcycle, which leads to a decrease in ATP synthesis and cell damage. CONCLUSIONS: Chronic exposition to Zn apparently induced adaptative mechanisms eliminating excess of the metal from the cells. These changes may directly inhibit intramitochondrial acetyl-CoA synthesis and its transport to cytoplasmic compartment, yielding impairment of cell viability and suppression their transmitter functions. Chronic neurons are more susceptible to increase extracellular concentrations of zinc than astrocytes. Supported by MNiSW projects MN 01-0108/08/248 and MUG fund ST-57.