Co-expression of D1R increases GHSR1a constitutive inhibition of CaV2.2 calcium currents

MC CARTHY CLARA INES; CORDISCO GONZALEZ, S.; RODRÍGUEZ, SILVIA S.; RAINGO JESICA

Mar del Plata

Congreso; XXXII Congreso de la Sociedad Argentina de Investigación en Neurociencias.; 2017

Sociedad Argentina de Investigación en Neurociencias.

Voltage-gated calcium channels (Cav) respond to depolarizations of the axon terminal, allowing calcium influx and the following release of neurotransmitters to the synaptic cleft. They are highly regulated points of neurotransmission. G protein coupled receptors (GPCR) signaling pathways are efficient Cav control mechanisms. The ghrelin receptor GHSR (growth hormone secretagogue receptor) is a GPCR that modulates presynaptic Cav (Cav2), constitutively reducing channel density and through agonist-evoked inhibition. Among GPCRs, GHSR has the highest known constitutive activity and the ability to heterodimerize with other GPCRs. It heterodimerizes with dopamine D1 receptor (D1R), another GPCR with agonist-evoked inhibition on Cav2. This interaction modifies their signaling pathways and physiological aspects, as GHSR alters D1R?s effects on memory processes. We investigated how GHSR/D1R co-expression modifies Cav2 regulation. Through patch clamp recordings on heterologous expression systems, we found that D1R expression increases Cav2.2 currents, whereas GHSR/D1R co-expression drastically reduces them. Cav2.2 current levels were same as control when D1R co-expressed with GHSR-A204E, a mutant lacking constitutive activity, suggesting current decrease is due to a raise in GHSR?s constitutive activity. Co-expression and individual expression of these receptors would have different effects on Cav channels, resulting in a wider range of action of these GPCRs over synapsis regulation.