Mechanisms shaping the slow nicotinic synaptic current at the motoneuron-renshaw cell synapse.
In spinal cord slices from newborn mice we have analyzed the kinetics of the EPSCs mediated by heteromeric nicotinic receptors at the motoneuron-Renshaw cell (MN-RC) synapse. The miniature EPSCs decay with a time constant of 13.0 ± 1.1 ms whereas the decay of the evoked EPSCs (eEPSCs) is biphasic, with time constants of 15.6 ± 0.8 and 124.8 ± 9.0 ms. The slow component becomes prominent during a repetitive stimulation, but its time constant is unchanged. It is selectively reduced by the addition of acetylcholinesterase (AChE), and thus appears to involve ACh spillover. The constancy of the slow time constant during a train is best explained by a local spillover activating high-affinity receptors. In many cells a fraction of the eEPSC originates in neighboring RCs and is transmitted by the low-pass filter of the gap junctions. The component transmitted electrically can be eliminated by meclofenamic acid, a blocker of gap junctions. The local spillover produced by a repetitive stimulation was compared with the long-range spillover produced by inactivation of AChE. The pharmacological inactivation of AChE by neostigmine caused the appearance of an ultra-slow (second range) decay component in eEPSCs and also a continuous inward current interpreted as resulting from a continuous ACh presence. In animals lacking functional AChE in the CNS (PRiMA(-/-) mice) the EPSCs resembled those observed in neostigmine but the steady inward current was much smaller, suggesting an adaptation to the absence of AChE.
Neurophysique et Physiologie, Université Paris Descartes, CNRS UMR 8119, Paris France. boris.lamotteincamps@parisdescartes.fr
Boris
B
Lamotte d'Incamps
Eric
E
Krejci
Philippe
P
Ascher
D000109:Acetylcholine / Q000378:metabolism / Q000502:physiology; D000110:Acetylcholinesterase / Q000235:genetics / Q000494:pharmacology; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D004558:Electric Stimulation / Q000379:methods; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D017629:Gap Junctions / Q000187:drug effects / Q000502:physiology; D007395:Interneurons / Q000187:drug effects / Q000502:physiology*; D008469:Meclofenamic Acid / Q000494:pharmacology; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology*; D009388:Neostigmine / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000235:genetics; D011978:Receptors, Nicotinic / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D002800:Cholinesterase Inhibitors; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011978:Receptors, Nicotinic; C486718:prima1 protein, mouse; D009388:Neostigmine; D008469:Meclofenamic Acid; D000110:Acetylcholinesterase; D000109:Acetylcholine