Differences in GABAA receptor subunit composition and sensitivity to ethanol in male and female hypothalamic neurons

MIR, F.; CAMBIASSO, M.J.; CARRER, H.F.; AGUAYO, L.G.

Huerta Grande - Córdoba

Congreso; II Reunión Conjunta de Neurociencias/XXV Reunión Anual de la Sociedad Argentina de Investigación en Neurociencias; 2010

Sociedad Argentina de Investigación en Neurociencias (SAN) y Taller Argentino de Neurociencias (TAN)

Pharmacological and electrophysiological properties of GABAA receptors are dependent on subunit conformation. Previous results from our lab revealed that the response to muscimol is greater in male hypothalamic neurons than female ones. To search for a sexually dimorphic subunit constitution of GABAA receptors, we conducted whole-cell patch clamp recordings in 2 or 9 DIV neurons. Responses to different GABA concentrations as well as the percentage of potentiation or inhibition of 10 µM GABA-elicited currents in the presence of allosteric modulators such as diazepam, alfaxalone, propofol, Zn, furosemide and ethanol were recorded. There were no statistical sex differences in those parameters. However, ethanol potentiated the GABAergic current only in female neurons. In addition, mRNA from 2 DIV sexually discriminated cultures was extracted and RT-PCR was performed in order to amplify GABAA receptor subunits. The analysis showed that most subunits were present in both sexes, but the alpha4 subunit was exclusive for females. Our data confirm that GABAA receptor subunits in hypothalamic neurons from E16 embryos are different in males and females even before the hormonal sexual differentiation. Supported by ANPCyT PICT26331 and 0456, CONICET PIP2010, MCyTCBA PID2008 and NIH RO1 15015