Figure 4.
Intercellular signaling mechanisms that alter cellular activity and clock gene expression within SCN neurons. A. SCN neurons express the VPAC2 receptor for VIP, which is a G-protein coupled receptor with seven transmembrane domains. Upon VIP binding to VPAC2, Gαs activates adenylyl cyclase, cAMP, PKA, and CRE-dependent transcription. B. Within the SCN both GABAA receptors and GABAB receptors are expressed. GABA binding to the ionotropic GABAA receptor allows for influx or efflux of Cl-, depending on [Cl-]i. In contrast, the metabotropic GABAB receptor is coupled to Gαi/o, which inhibits adenylyl cyclase. C. The receptors for both AVP and GRP are Gαq coupled receptors that stimulate phospholipase C (PLCβ), which in turn activates phosphatidylinositol 4,5-bisphosphate (PIP2) to cause diacyl glycerol (DAG)-mediated activation of protein kinase C (PKC) and inositol triphosphate (IP3)-induced release of intracellular calcium stores. Intracellular release of calcium activates Calmodulin (CaM), which stimulates Ca2+/ calmodulin-dependent protein kinase (CaMK). Due to the expression of CRE-elements in Period genes, changes in the intracellular signaling cascades illustrates in A-C can alter the function of the molecular clock.