IFIBYNE   05513
INSTITUTO DE FISIOLOGIA, BIOLOGIA MOLECULAR Y NEUROCIENCIAS
Unidad Ejecutora - UE
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
Reunión:
Congreso; IRCN First 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 medicationwhich was initially synthesized as a GABA analogous but strikingly hadno effect on its receptors. The primary high-affinity binding site for PGBis the α2-δ auxiliary subunit of voltage-gated calcium channels but thecellular and molecular details of its action are completely unknown. Themain objective of this work is to understand the effect of PGB at the mouseneuromuscular junction and to characterize its modulation on vesicularrelease and recycling. Experiments were performed on the levator aurismuscle of Swiss mice and fluorescence microscopy of FM2-10 labeledsynaptic vesicles were used to reach our aim. We studied the effect of PGBat two different concentrations on the distaining of a full neuromuscularterminal FM2-10 loaded. Results showed that PGB 1mM treatment held upthe kinetic decay significantly. The fluorescence distaining was fitted to abiexponential function that models first-order release processes when twodifferent time constants are involved. These time constants are associatedto different vesicle pools of different size. Both time constants augmentedwith the presence of the drug and the size of the fast pool increased versusthe control at 1mM concentration. PGB 100 µM had no effect on thedistaining decay suggesting dose response behaviour. To study whetherPGB is altering both P/Q and L channels, we performed experimentswith the L channel blocker nitrendipine. In addition, electrophysiologicalexperiments will be done to contrast the results obtained with imagingtechnique. All this evidence suggests that PGB acts presynaptically reducingneurotransmitter release.