Role of Ca2+ in induction of neurotransmitter-related gene expression by butyrate

We examined the effect of butyrate on neurotransmitter-related gene expression and calcium homeostasis in PC12 cells. Pretreatment with Ca 2+ chelators (EGTA or BAPTA-AM) attenuated the butyrate-triggered accumulation of TH and ppEnk mRNA indicating that Ca 2+ plays a role in butyrate-induced regulation of neuronal genes. Butyrate alone did not alter intracellular Ca 2+ levels as determined by Fura-PE3 fluorescence; however, pretreatment with butyrate (18-24 h) reduced the first Ca 2+ peak and prevented the second sustained rise in [Ca 2+ ] i as induced by nicotine or ryanodine. In contrast, butyrate had no effect on Ca 2+ transients when added shortly before or during nicotine or ryanodine stimulation. These results suggest that chronic butyrate exposure can modulate cell responses by affecting intracellular Ca 2+ signaling.