Up-regulation of L-Type Ca2+ Channel Associated with the Development of Elevated K+-Mediated Survival of Superior Cervical Ganglion Cells in Vitro

Abstract

We have previously shown that elevated K+-mediated neuronal survival correlates well with a sustained increase in cytoplasmic Ca2+ ([Ca2+]i) through the opening of L-type Ca2+ channels. Elevated K+ (40 mM), however, failed to support the survival of superior cervical ganglion (SCG) cells freshly isolated from newborn rats, while another depolarizing agent, veratridine, was able to do so, suggesting that elevated K+-mediated Ca2+ influx occurs in a stage-dependent manner. Indeed, sustained levels of [Ca2+]i in response to high K+ remained low (91 nM) in these neurons, but became elevated (238 nM) in SCG neurons which had been exposed to nerve growth factor (NGF) for 5-7 days and were capable of responding to elevated K+ by survival. Semi-quantitative PCR measurements of L-type Ca2+ channel mRNA revealed that this transcript increased dramatically during incubation with NGF for 3 days and reached a plateau level at Day 5 (seven-fold per surface area or nine-fold per total volume compared to that at Day 1). These findings show that NGF-mediated up-regulation of the expression of L-type Ca2+ channel mRNA correlates with the development of elevated K+-mediated neuronal survival in vitro and suggest its involvement in coordinate strengthening of pre- and postganglionic synapses in rat SCG neurons.