title: Dual Ca2+ modulation of glycinergic synaptic currents in rodent hypoglossal motoneurones.
abstract: Glycinergic synapses are implicated in the coordination of reflex responses, sensory signal processing and pain sensation. Their activity is pre- and postsynaptically regulated, although mechanisms are poorly understood. Using patch-clamp recording and Ca2+ imaging in hypoglossal motoneurones from rat and mouse brainstem slices, we address here the role of cytoplasmic Ca2+ (Ca(i)) in glycinergic synapse modulation. Ca2+ influx through voltage-gated or NMDA receptor channels caused powerful transient inhibition of glycinergic IPSCs. This effect was accompanied by an increase in both the failure rate and paired-pulse ratio, as well as a decrease in the frequency of mIPSCs, suggesting a presynaptic mechanism of depression. Inhibition was reduced by the cannabinoid receptor antagonist SR141716A and occluded by the agonist WIN55,212-2, indicating involvement of endocannabinoid retrograde signalling. Conversely, in the presence of SR141716A, glycinergic IPSCs were potentiated postsynaptically by glutamate or NMDA, displaying a Ca2(+)-dependent increase in amplitude and decay prolongation. Both presynaptic inhibition and postsynaptic potentiation were completely prevented by strong Ca(i) buffering (20 mm BAPTA). Our findings demonstrate two independent mechanisms by which Ca2+ modulates glycinergic synaptic transmission: (i) presynaptic inhibition of glycine release and (ii) postsynaptic potentiation of GlyR-mediated responses. This dual Ca2(+)-induced regulation might be important for feedback control of neurotransmission in a variety of glycinergic networks in mammalian nervous systems.
authors.affiliation: Institut de Neurobiologie de la Méditerranée, INSERM U29, 163, route de Luminy, 13273 Marseille cedex 09, France.
authors.forename: Marat
authors.initials: M
authors.lastname: Mukhtarov
authors.forename: Davide
authors.initials: D
authors.lastname: Ragozzino
authors.forename: Piotr
authors.initials: P
authors.lastname: Bregestovski
mesh_terms: D000818:Animals; D048588:Benzoxazines; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism; D018698:Glutamic Acid / Q000494:pharmacology; D005998:Glycine / Q000378:metabolism*; D007002:Hypoglossal Nerve / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D009025:Morpholines / Q000494:pharmacology; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism*; D016202:N-Methylaspartate / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D009433:Neural Inhibition; D010880:Piperidines / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D043882:Receptors, Cannabinoid / Q000187:drug effects; D018009:Receptors, Glycine / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism; D000077285:Rimonabant; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
chemical_list: D048588:Benzoxazines; D063385:Cannabinoid Receptor Modulators; D009025:Morpholines; D009281:Naphthalenes; D010880:Piperidines; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D016202:N-Methylaspartate; D000077285:Rimonabant; D002118:Calcium; D005998:Glycine