Modulation of CaV1.3 activity by melanocortin receptor type 4 (MC4R)

FRANCINA AGOSTI; E JAVIER LOPEZ SOTO; MARIO PERELLO; JESICA RAINGO

Huerta grande Cordoba

Congreso; XXVI Congreso Anual de la Sociedad Argentina de Investigación en Neurociencia; 2011

MC4R mutations are, by far, the most common cause of monogenic obesity in humans. It has been shown that MC4R is highly expressed in the hypothalamic paraventricular nucleus (PVN), where it increases expression of appetite related-genes. The mechanisms by which MC4R regulates gene expression are unclear. Calcium influx through L-type calcium channels induces gene expression in neurons. The PVN neurons express the L channel isoform, CaV1.3, which is activated by negative potentials and has a narrow distribution in the brain. Here, we tested if MC4R regulates CaV1.3 activity using the patch clamp technique in HEK293 cells. We developed an in vitro system co-expressing CaV1.3, the auxiliary subunits and a MC4R plasmid with the soluble GFP sequence. We found that MC4R co-expression did not modify the CaV1.3 biophysical properties, such as voltage activation and kinetic. However, we observed an inverse correlation between the amount of transfected MC4R cDNA and CaV1.3 current levels, suggesting an effect of MC4R basal activity on CaV1.3 function. In line with this possibility, we found that mu-opioid receptor, which has no basal activity, did not affect CaV1.3 current levels. Our results suggest that CaV1.3 could be a target of MC4R to regulate gene expression in PVN neurons.