Coactivation of secretogranin-II and BDNF genes mediated by calcium signals in mouse cerebellar granule cells

Abstract

In primary culture of mouse cerebellar granule cells, the brain-derived neurotrophic factor (BDNF) gene is activated in an activity-dependent manner, accompanying Ca 2+ influx into neurons through voltage-dependent calcium channels (VDCCs). In this study, we investigated the inducibility of secretogranin-II (Sg-II) gene in terms of Ca 2+ signals evoked via VDCCs, by a comparison with BDNF and c- fos genes. Deprivation and subsequent induction of membrane depolarization by lowering and reelevating the extracellular concentration of potassium chloride (KCl), respectively, led to an decrease and then an increase in the Sg-II, BDNF and c- fos mRNA expression. The increase in Sg-II mRNA expression was detected as early as but was slower than that of BDNF one. The increase in Sg-II mRNA expression was induced depending upon the extracellular Ca 2+ and inhibited by nicardipine, indicating a requirement of Ca 2+ influx through VDCCs for the Sg-II as well as BDNF gene induction. Inhibition of de novo protein synthesis by cycloheximide did not affect the Sg-II induction. The response of Sg-II gene to the changes in extracellular KCl concentration was the same as that of BDNF but different from that of c- fos gene. Thus, Sg-II gene is coactivated with BDNF gene in response to the intracellular Ca 2+ signals evoked via Ca 2+ influx through VDCCs.