GHRELIN RECEPTOR CONSTITUTIVE ACTIVITY REDUCES SURFACE EXPRESSION OF VOLTAGE-GATED CALCIUM CHANNELS IN A CAVβ DEPENDENT MANNER

MUSTAFÁ ER; LÓPEZ SOTO EJ; MARTÍNEZ DAMONTE V; RODRÍGUEZ, SILVIA S.; LIPSCOMBE, DIANE; RAINGO, JESICA

Buenos Aires

Congreso; JOINT MEETING OF BIOSCIENCE SOCIETIES; 2017

Sociedad Argentina de Investigación Clínica

Voltage gated calcium channels (CaV) couple plasma membranevoltage changes to calcium influx, triggering calcium dependent processes.This sequence of fact is crucial for shaping neuronal activity.Several CaV subtypes exist and they have different time- and place-specificfunctions in neurons. Thus, great effort has been devotedto determine what elements can control CaV activity in neurons.In this context, many G protein coupled receptors (GPCR) activatedcascades have been detected as powerful CaV activity modulators.On the other hand, data about the control of trafficking and density ofCaV subtypes at specific location on the neuronal plasma membraneare scarce. Here we describe that a GPCR that is constitutively active(GHSR1a) in absence of its agonist (ghrelin) significantly inhibitsthe forward trafficking to the plasma membrane of several CaV subtypes(low- and high- voltage activated CaV) and consequently CaVcurrents. We found that the mechanism implies retention of the channelcomplexes at the endoplasmic reticulum and the requirement ofauxiliary subunit CaVβ. This was demonstrated in both hypothalamicprimary neuronal cultures and in heterologous expression systems,using patch-clamp electrophysiology, live fluorescent- and confocalmicroscopyto examination the subcellular locations of taggedproteins. We reported significant differences when calculated p-value