| Abstract No.: | B-B2061 |
| Country: | Canada |
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| Title: | NO-DEPENDENT GLUTAMATERGIC MODULATION AT THE CHOLINERGIC VERTEBRATE NEUROMUSCULAR JUNCTION. |
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| Authors/Affiliations: | 1 Audrée Pinard*; 1 Joanne Vallée; 1 Richard Robitaille;
1 Université de Montréal, QC, Canada
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| Content: | The well established concept of purely cholinergic synaptic transmission at the vertebrate neuromuscular junction (NMJ) was recently challenged by studies showing the presence of glutamate and nitric oxide (NO). The synaptic functions of these two neuroactive compounds on neuromuscular transmission remain however elusive. The aim of the present study is to identify the roles of glutamate and nitric oxide on synaptic transmission and to determine the cellular mechanisms involved in this modulation. Using electrophysiological recordings, calcium and nitric oxide imaging, we were able to establish that glutamate and nitric oxide regulate the preponderant form synaptic plasticity phenomenon acting on the NMJ, short-term synaptic depression. We showed that NO and glutamate not only similarly reduce synaptic transmission but also have comparable effects on synaptic depression. These similarities in the properties of glutamate and NO effects on synaptic transmission reveal an important aspect of their respective roles at the NMJ. Indeed, we were able to show that the effect of one depends on the presence of the other. Blockade of NO production by inhibiting its synthesising enzyme, nitric oxide synthase (NOS), leads to a total absence of glutamate effect on synaptic transmission and depression. Based on this result, we investigated further the mechanisms involved in this glutamate-NO cooperation. Immunohistochemical and electrophysiological data indicate that glutamate receptors involved in glutamate action are of the mGlu type and located at the end-plate. On the other hand, complementary data indicate that glutamate, just as NO, acts presynaptically. This apparent discrepancy in glutamate receptor localisation and its presynaptic locus of action, argues further for the importance of NO-glutamate cooperation at the NMJ where NO could mediate the long-distance effect of glutamate to the nerve terminals. Using the visualisation of NO production we found that postsynaptic mGluR activation leads to the production of NO that retrogradely diffuses to the presynaptic terminal. Lastly, we investigated the whether the mGluR activation of NO production was calcium-dependent. Iontophoretic injection of the calcium chelator BAPTA in muscle fibres totally prevented mGluR agonist (trans-ACPD) effect on synaptic transmission, the effect of the mGluR antagonist, MCPG, on synaptic depression and prevented all fluorescent changes of the NO fluorescent indicator. This result confirms that calcium is a key element mediating the cross-talk between mGluR and NOS activation. Taken together, the results obtained in this study provide an innovative view of the neuromuscular transmission now including glutamate and NO as new synaptic players offering an additional refinement of the final input leading to muscle contraction. |
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