IBCN   20355
INSTITUTO DE BIOLOGIA CELULAR Y NEUROCIENCIA "PROFESOR EDUARDO DE ROBERTIS"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Effects of muscarinic toxins 1 and 2 on CA1 synapses of rat hippocampus
Autor/es:
M. V. OBERHOLZER; E. KORNISIUK; F. J. URBANO; C. CERVEÑANSKY; D. JERUSALINSKY
Lugar:
San Diego, California, USA
Reunión:
Congreso; 40th Annual Meeting Neuroscience 2010; 2010
Institución organizadora:
Society for Neuroscience
Resumen:
Muscarinic toxins 1 and 2 (MT1 and MT2) from Green Mamba snake venom act as selective M1 muscarinic receptor agonists and M4 receptor antagonists. MT2 has 4-fold higher affinity for M1 than for M4 receptor. Both toxins improved memory in a one-step inhibitory-avoidance footshock task in rats when injected into the hippocampus immediately after training. MT1 enhanced basal transmission in whole-cell voltage-clamp recordings in CA1 pyramidal neurons in cultured slices of rat hippocampus. MT2 enhanced field potentials in CA1 of rat hippocampal fresh slices and also decreased paired pulse facilitation. MT1 was tested in field potential recordings. It enhanced basal neurotransmission by 45 ± 4 %, but did not have any significant effect on paired pulse facilitation. Radioligand binding assays in rat hippocampal synaptosomal membranes were performed in order to evaluate MT2 and MT1 inhibition on the muscarinic ligand 3H-N-methylscopolamine (3H-NMS) and the a adrenergic ligand 3H-prazosin (3H-PRZ) binding. Both toxins inhibited 3H-NMS binding with Ki = 180 ± 7 nM for MT1, and Ki = 380 ± 12 nM for MT2, with maximal inhibitions of 49 ± 5 % and 67 ± 7 %, respectively. And they inhibited 3H-PRZ binding with Ki = 83 ± 3 nM for MT1 and Ki = 292 ± 11 nM for MT2, with maximal inhibitions of 34 ± 4 % and 35 ± 7 %, respectively. MT1 and MT2 have significant affinities for both a adrenergic and muscarinic receptors; furthermore, MT1 shows slightly higher affinity for adrenergic receptors. PRZ 10 mM was also tested in field potential recordings and there was a facilitatory effect of 16 ± 3 % on basal transmission. However, the effect of MT2 was effectively blocked by both pirenzepine and atropine, showing the M1 muscarinic subtype involvement in the phenomenon. Since PRZ inhibited 3H-NMS binding with a Ki = 5,1 ± 1,2 mM, we speculate that the PRZ facilitatory effect on field potential recordings could be associated to muscarinic stimulation.