Two-component action of ATP on transmitter release from the motor nerve endings at the neuromuscular junction

Abstract

s / Journal of Physiology Paris 99 (2006) 245–278 255 evoked synaptic responses, muscle twitch and tetanic tensions. In addition, complementary information was obtained by confocal laser scanning microscopical examination of the endplate region of the various transgenic muscles in order to determine the characteristics of muscle nicotinic ACh receptor clustering. The results obtained indicate that focally recorded miniature endplate currents (MEPC) exhibit a prolonged decay time in all transgenic mice examined with the exception of PRiMA / mutant muscles in which MEPCs were not affected. Complementary morphological examination revealed that there is an important remodeling and different clustering of muscle nicotinic ACh receptors at junctions lacking AChE activity in which MEPCs were prolonged. These results will be discussed in terms of physiological adaptation or compensation for the absence of AChE activity, and in relation to the expression of AChE and BChE at the neuromuscular junction. Supported by the AFM and by ACI # 0220530. doi:10.1016/j.jphysparis.2005.12.035 Camp, S., Zhang, L., Marquez, M., et al., 2004. In: Inestrosa, N.C., Campos, E.O. (Eds.), Cholinesterases in the Second Millennium: Biomolecular and Pathological Aspects. p. 43. Feng, G., Krejci, E., Molgo, J., Cunningham, J.M., Massoulie, J., Sanes, J.R., 1999. Genetic analysis of collagen Q: roles in acetylcholinesterase and butyrylcholinesterase assembly and in synaptic structure and function. J. Cell. Biol. 144, 1349–1360. Minic, J., Chatonnet, A., Krejci, E., Molgo, J., 2003. Butyrylcholinesterase and acetylcholinesterase activity and quantal transmitter release at normal and acetylcholinesterase knockout mouse neuromuscular junctions. Br. J. Pharmacol. 138, 177–187. Perrier, A.L., Massoulie, J., Krejci, E., 2002. PRiMA: the membrane anchor of acetylcholinesterase in the brain. Neuron 33 (2), 275–285. Xie, W., Stribley, J.A., Chatonnet, A., Wilder, P.J., Rizzino, A., McComb, R.D., Taylor, P., Hinriches, S.H., Lockridge, O., 2000. Postnatal developmental delay and supersensitivity to organophosphate in genetargeted mice lacking acetylcholinesterase. J. Pharmacol. Exp. Ther. 293, 896–902. The possible contribution of mast cells in the methylmercury-evoked effects Elizabeth E. Graevskaya Biophysical Department, Biological Faculty, Lomonosov Moscow State University, Vorobevy Gory, Moscow 119992, Russia E-mail address: graevsk@biophys.msu.ru Methylmercury (MeHg) is a well-established significant environmental neurotoxic agent, known as the cause of Minamata disease (IPCS, 1990). As it is known MeHg penetrates the blood-brain barrier to cause severe neurological symptoms in human beings and experimental animals, destructs neurons and glial cells, and disrupts neuronal migration. At the same time, increasing evidence indicates that neuroimmune interactions, including neuroinflammatory processes, may involve also mast cells. Mast cells and their transmitter content play a role in triggering an immune response in the brain. In our study we tried to define the possible contribution of mast cells in the development of methylmercury-evoked effects. As a model we used rat peritoneal mast cells, because it is easier to get the requisite amount of mast cells for measuring modifications of transmitter release. We investigated the effects of MeHg on mast cell degranulation induced by non-immunological stimuli (the selective inductor of histamine release): the compound 48/80 and the calcium ionophore A23187, both in vivo and in vitro. Eight, 12 and 15 days after administration of MeHg (10 mg/kg/day) we observed that the calcium ionophore A23187and 48/80-induced histamine release gradually decreased. Mast cells from rat exposed 24 or 72 h to a single dose of MeHg (20 mg/kg) showed a significant inhibition of the A23187-stimulated histamine secretion, but no change in the compound 48/ 80-stimulated release. In vitro incubation of peritoneal mast cells with MeHg alone (10 –10 6 M) did not induce mast cell degranulation, but modified the activation of mast cells by compound 48/80 and calcium ionophore A23187. We observed a facilitation of stimulated secretion by prior incubation with low dose of MeHg (10 8 M) and an inhibition at 10 6 M MeHg. These results show that MeHg treatment can modify mast cell function in vivo and in vitro and provide insight into the understanding what role this cell has in the pathogenesis of Minamata disease-connected disorders. doi:10.1016/j.jphysparis.2005.12.036 International Programm of Chemical Safety (IPCS), 1990. Environmental health criteria 101, methylmercury. World Health Organization, Geneva, p. 144. Effect of delta sleep inducing peptide on NMDA and GABA evoked ion currents in cortical, cerebellar and hippocampal