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

EDUARDO JAVIER LOPEZ SOTO; DIANE LIPSCOMBE; VALENTINA MARTÍNEZ DAMONTE ; JESICA RAINGO; MUSTAFÁ EMILIO ROMÁN,; SILVIA S. RODRÍGUEZ

Washington

Congreso; 47th annual meeting of the Society for Neuroscience; 2017

Society for Neuroscience

Voltage gated calcium channels (CaV) couple plasma membrane voltage 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-specific functions in neurons. Thus, great effort has been devoted to determine what elements can control CaV activity in neurons. In this context, many G protein coupled receptors (GPCR) activated cascades have been detected as powerful CaV activity modulators. On the other hand, data about the control of trafficking and density of CaV subtypes at specific location on the neuronal plasma membrane are scarce. Here we describe that a GPCR that is constitutively active (GHSR1a) in absence of its agonist (ghrelin) significantly inhibits the forward trafficking to the plasma membrane of several CaV subtypes (low- and high- voltage activated CaV) and consequently CaV currents. We found that the mechanism implies retention of the channel complexes at the endoplasmic reticulum and the requirement of auxiliary subunit CaVβ. This was demonstrated in both hypothalamic primary neuronal cultures and in heterologous expression systems, using patch-clamp electrophysiology, live fluorescent- and confocal- microscopy to examination the subcellular locations of tagged proteins. We reported significant differences when calculated p-value