INVESTIGADORES
DI GUILMI Mariano Nicolas
congresos y reuniones científicas
Título:
Pregabalin effect on transmitter release at the mouse Neuromuscular Junction
Autor/es:
LÓPEZ ME, PERISINOTTI PP, DI GUILMI MN AND UCHITEL OD.
Lugar:
Huerta Grande, Cordoba, Argentina
Reunión:
Congreso; 1st. Joint Meeting of the Argentine Society for Neurosciences (SAN) and the Argentine Workshop in Neurosciences (TAN); 2009
Resumen:
Pregabalin (PGB) is an anticonvulsant and analgesic medication
which was initially synthesized as a GABA analogous but strikingly had
no effect on its receptors. The primary high-affinity binding site for PGB
is the α2-δ auxiliary subunit of voltage-gated calcium channels but the
cellular and molecular details of its action are completely unknown. The
main objective of this work is to understand the effect of PGB at the mouse
neuromuscular junction and to characterize its modulation on vesicular
release and recycling. Experiments were performed on the levator auris
muscle of Swiss mice and fluorescence microscopy of FM2-10 labeled
synaptic vesicles were used to reach our aim. We studied the effect of PGB
at two different concentrations on the distaining of a full neuromuscular
terminal FM2-10 loaded. Results showed that PGB 1mM treatment held up
the kinetic decay significantly. The fluorescence distaining was fitted to a
biexponential function that models first-order release processes when two
different time constants are involved. These time constants are associated
to different vesicle pools of different size. Both time constants augmented
with the presence of the drug and the size of the fast pool increased versus
the control at 1mM concentration. PGB 100 µM had no effect on the
distaining decay suggesting dose response behaviour. To study whether
PGB is altering both P/Q and L channels, we performed experiments
with the L channel blocker nitrendipine. In addition, electrophysiological
experiments will be done to contrast the results obtained with imaging
technique. All this evidence suggests that PGB acts presynaptically reducing
neurotransmitter release.