INIBIBB   05455
INSTITUTO DE INVESTIGACIONES BIOQUIMICAS DE BAHIA BLANCA
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Neurotransmitter GABA activates muscle but not a7 nicotinic receptors
Autor/es:
DIONISIO, L.; BERGÉ, I.; BRAVO, M.; ESANDI, M.C.; BOUZAT, C.
Lugar:
Sierra de la Ventana, Bs As.
Reunión:
Congreso; Congreso de la Sociedad Argentina de Biofísica; 2014
Institución organizadora:
SAB
Resumen:
Cys-loop receptors are neurotransmitter-activated ion channels
involved in synaptic and extrasynaptic transmission in the brain
and are also present in non-neuronal cells. As GABAA and nicotinic
receptors (nAChR) belong to this family, we explored by
macroscopic and single-channel recordings if the inhibitory
neurotransmitter GABA has the ability to activate excitatory
nAChRs. GABA differentially activates nAChR subtypes. It
activates muscle nAChRs, with maximal peak currents of about 10
% of those elicited by ACh and 15-fold higher EC50 with respect to
ACh. At the single-channel level, the weak agonism is revealed by
the requirement of 20-fold higher concentration of GABA for
detectable channel openings, a major population of brief openings,
and absence of clusters of openings when compared to ACh.
Mutations at key residues of the principal binding-site face of
muscle nAChRs (αY190 and αG153) affect GABA-activation
similarly as ACh-activation whereas a mutation at the
complementary face (εG57) shows a selective effect for GABA.
Studies with subunit-lacking receptors show that GABA can
activate muscle nAChRs through the α/δ interface. Interestingly,
single-channel activity elicited by GABA is similar to that elicited by
ACh in gain-of-function nAChR mutants associated to congenital
myasthenic syndromes, which could be important in the
progression of the disorders due to steady exposure to serum
GABA. In contrast, GABA cannot elicit single-channel or
macroscopic currents of α7 or the chimeric α7-5HT3A receptor, a
feature important for preserving an adequate excitatory/inhibitory
balance in the brain as well as for avoiding activation of nonneuronal
receptors by serum GABA.