Abstract
Voltage-gated Ca(2+) (Ca(V)) channels couple membrane depolarization to Ca(2+) influx, triggering a range of Ca(2+)-dependent cellular processes. Ca(V) channels are, therefore, crucial in shaping neuronal activity and function, depending on their individual temporal and spatial properties. Furthermore, many neurotransmitters and drugs that act through G protein coupled receptors (GPCRs), modulate neuronal activity by altering the expression, trafficking, or function of Ca(V) channels. GPCR-dependent mechanisms that downregulate Ca(V) channel expression levels are observed in many neurons but are, by comparison, less studied. Here we show that the growth hormone secretagogue receptor type 1a (GHSR), a GPCR, can inhibit the forwarding trafficking of several Ca(V) subtypes, even in the absence of agonist. This constitutive form of GPCR inhibition of Ca(V) channels depends on the presence of a Ca(V)β subunit. Ca(V)β subunits displace Ca(V)α(1) subunits from the endoplasmic reticulum. The actions of GHSR on Ca(V) channels trafficking suggest a role for this signaling pathway in brain areas that control food intake, reward, and learning and memory.