INVESTIGADORES
CALVO Daniel Juan
congresos y reuniones científicas
Título:
Homomeric rho1 GABAC receptor function is potentiated by S-nitrosylation
Autor/es:
GASULLA J; BELTRÁN GONZALEZ A; CALVO, DANIEL J.
Lugar:
Huerta Grande Córdoba
Reunión:
Congreso; XXVI Reunión Nacional Sociedad Argentina de Investigación en Neurociencias (SAN); 2011
Institución organizadora:
Sociedad Argentina de Investigación en Neurociencias
Resumen:
Homomeric ρ1 GABAC receptor function is
potentiated by S-nitrosylation
Javier Gasulla, Andrea Beltrán González and
Daniel J. Calvo
INGEBI-CONICET. Argentina.
Nitric Oxide (NO) is a gas messenger produced in neurons that can modulate
the activity of neurotransmitter receptors. We have previously shown that NO potentiates
GABAC receptor function. Earlier
studies reported the S-nitrosylation of cysteine residues in NMDA and GABAA
receptors by NO. Thus, we examined if GABAC receptors
can undergo analogous modifications.
Homomeric ρ1 GABAC receptors (GABAρ1R) were expressed in oocytes and GABA-evoked responses
electrophysiologically recorded in the presence or absence of the NO donor
DEA/NONOate (DEA). GABAρ1 responses were significantly enhanced in a
dose-dependent, fast and reversible manner by DEA. The specific NO scavenger
CPTIO prevented these effects. Each GABAρ1R subunit contains
three cysteine residues, namely: two extracellular at the cys-loop (C177 and
C191) and one intracellular (C364). Site directed mutagenesis of the C177 and C191 renders non-functional receptors,
but C364 can be safely exchanged by alanine. The chemical protection of these cysteine residues by sulfhydryl reagents (NEM,
MTSEA) prevented DEA effects on GABAρ1R. Meanwhile, wild type receptors and mutant GABAρ1C364AR were similarly potentiated by DEA. These results suggest that NO enhances GABAC receptor
function through S-nitrosylation occurring at the cys-loop.