INVESTIGADORES
DIONISIO Leonardo Raul
congresos y reuniones científicas
Título:
Crosstalk between cholinergic and gabaergic systems
Autor/es:
BRAVO, M.; DIONISIO, L.; SPITZMAUL, G.; BOUZAT, C.
Lugar:
Huerta Grande, Córdoba
Reunión:
Congreso; I Reunión Conjunta de Neurociencias; 2009
Institución organizadora:
SAN-TAN
Resumen:
Cys-loop receptors are pentameric neurotransmitter-activated ion
channels that mediate fast synaptic transmission throughout the nervous system.
They include excitatory receptors, such as the nicotinic cholinergic (AChR) and
serotonin type 3 receptors (5-HT3), and inhibitory receptors
activated by GABA or glycine. Given the homology between members of this family we
evaluated if GABAergic agonists can activate nicotinic cholinergic receptors.
In the presence of GABA (> 1 µM), single-channel openings from the muscle
AChR are readily detected. Even at high GABA concentrations, openings do not
appear in typical clusters as observed in ACh-activated channels, indicating
that GABA is a low-efficacy agonist. The presence of GABA does not affect the
channel properties of ACh-activated channels. We also studied activation by
GABA of muscle AChRs carrying a mutation in aG153, which has been shown to decrease the dissociation rate of ACh (Sine et al., 1995). GABA activation
is enhanced in the aG153S and aG153E mutants, indicating that this residue is involved in the activation by both
neurotransmitters.
In silico studies show
that in the muscle AChR, GABA docks into the ACh-binding site, though it
interacts with different residues when compared to ACh. However, no docking
into the binding site is observed in the a7 AChR, in agreement with the lack of activation.
In conclusion, we determine that GABA is not capable of activating
neuronal a7 AChRs but it acts as a partial agonist of the muscle AChR.