Presynaptic calcium channels regulation by ghrelin receptor (GHSR1a) activity

LOPEZ SOTO JE; RODRÍGUEZ SS; AGOSTI F; PERELLO M; RAINGO J

Cancún, Quintana Roo

Congreso; I Congreso de la Federación de Asociaciones Latinoamericanas y del Caribe de Neurociencias; 2012

Federación de Asociaciones Latinoamericanas y del Caribe de Neurociencias

The growth hormone secretagogue receptor type 1a (GHSR1a) is the only site of action identified until this moment of ghrelin hormone. Through GHSR1a, ghrelin acts in specific neuronal hypothalamic circuit inducing an increase in food intake, and ultimately an increase in body weight. GHSR1a belongs to G protein coupled receptor family and its activation is mediated by agonist and constitutively. In neurons, GHSR1a regulates the increase of Ca2+ ion concentration; however its relation with calcium channels is not completely understood. We assayed basal and evoked activity of GHSR1a on modulation of presynaptic calcium channels. We performed whole-cell patch clamp recordings in tsA201 cells expressing GHSR1a and presynaptic calcium channels (CaV2.1 and CaV2.2). We found that the amount of GHSR1a cDNA plasmid used during the transfection inversely correlates with the percentage of transfected cells with detectable CaV2.2 and CaV2.1 basal current. Of note, the percentage of transfected cells with detectable CaV2.2 basal currents is not affected by a mutated form of GHSR1a that lacks constitutive activity. Also, we found that ghrelin treatment inhibits CaV2.2 basal current levels in a concentration-dependent manner (16.0±2.1 and 48.8±3.3 % of total CaV2.2 current for ghrelin 100 and 500 nM, respectively), however evoked GHSR1a activity is not affect CaV2.1 current. This specific ghrelin-induced inhibition on CaV2.2 current is partially washable and fully independent of the applied voltage. We conclude that basal GHSR1a activity inhibits presynaptic calcium channels, although evoked GHRS1a activity only inhibits specifically CaV2.2. These effects could count for the physiological effect of ghrelin at presynaptic terminals. We are currently investigating the pathways mediating this effect and the modulation of these pathways by newly synthesized agonist and antagonist of GHSR1a.