Figure 10.

Schematic description of receptors and pathways known to be involved in IP₃-generated calcium signals and early gene regulation in muscle cells. The signaling pathway begins at the DHPR located in the T-tubule membrane; a heterotrimeric G protein with a Gi type subunit is proposed to interact with DHPR and to activate PLC to produce IP₃ and DAG. IP₃ will diffuse into the cytosol and reach IP₃Rs located both at the SR membrane and at the nuclear envelope. Calcium release will occur independently into both cytosol and nucleoplasm and several calcium-dependent mechanisms will be activated. ERKs 1/2 will be phosphorylated in the cytosol and phosphorylated CREB (P-CREB) will increase inside the nucleus. Transcription of early genes such as c-jun will increase after P-CREB activation of a CRE box located upstream. All of the above steps are based on published data. Roles for the Ras-raf pathway upstream of ERKs and for PKC, activated by DAG as nuclear coactivator of CREB are postulated based on inhibition experiments (unpublished data). Red arrows denote activation and blue arrows indicate release.