Convergent effects of Ca²⁺ and cAMP signals on the expression of immediate early genes in neurons

How the expression of immediate early genes (IEGs) is controlled in response to neurotransmissions is unknown. Using cultured rat cortical cells, we investigated the expression of IEGs regulated by Ca²⁺ and/or cAMP signals. The expression of c-fos was transiently induced by treatment of cells with high potassium (high K⁺), which evoked depolarization, or forskolin, an adenylate cyclase activator. c-fos expression was persistently and synergistically induced by simultaneous treatment with high K⁺ and forskolin via cAMP-response element (CRE). Microarray analysis indicated the expression profiles of IEGs caused by depolarization in the presence or absence of forskolin. When a novel index was included to investigate the profile of IEGs, we found that high K⁺-induced expression of IEGs was stimulatory or negatively changed in the presence of forskolin, suggesting distinct convergent effects of Ca²⁺ and cAMP signals on the expression of IEGs.