title: Nitric oxide selectively tunes inhibitory synapses to modulate vertebrate locomotion.
abstract: We have explored the possible modulation by nitric oxide (NO) of inhibitory synaptic transmission mediated by either glycine or GABA during episodes of rhythmic fictive swimming in postembryonic Xenopus laevis tadpoles. Extracellular ventral-root recordings suggest a stage-dependent increase in the reliability and extent of the NO donor S-nitroso-n-acetylpenicillamine (SNAP; 0.1-1 mm) to inhibit swimming by reducing the frequency and shortening the duration of swim episodes. These effects of SNAP on the swimming rhythm at both developmental stages are corroborated by intracellular recordings from presumed motor neurons with sharp microelectrodes, which also suggest that NO inhibits swimming by facilitating both glycinergic and GABAergic inhibition. However, we found no evidence for NO modulation of the excitatory drive for swimming. In addition to presynaptic effects on inhibitory transmitter release, a pronounced postsynaptic membrane depolarization ( approximately 5-10 mV) and conductance decrease ( approximately 10-20%) are associated with bath application of SNAP. Hence, NO exerts inhibitory effects on swimming through multiple but selective actions on both the electrical properties of spinal neurons and on particular synaptic interconnections. The presynaptic and postsynaptic effects of NO act in concert to tune inhibitory synapses.
authors.affiliation: School of Biology, Division of Biomedical Sciences, University of St. Andrews, St. Andrews, FIFE KY16 9TS, United Kingdom.
authors.forename: David L
authors.initials: DL
authors.lastname: McLean
authors.forename: Keith T
authors.initials: KT
authors.lastname: Sillar
mesh_terms: D000367:Age Factors; D000818:Animals; D004305:Dose-Response Relationship, Drug; D018756:GABA Antagonists / Q000494:pharmacology; D005998:Glycine / Q000037:antagonists & inhibitors / Q000378:metabolism; D018684:Glycine Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D007814:Larva / Q000502:physiology; D008124:Locomotion / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism* / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D013550:Swimming / Q000502:physiology; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology; D014982:Xenopus laevis; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D018756:GABA Antagonists; D018684:Glycine Agents; D020030:Nitric Oxide Donors; D009569:Nitric Oxide; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; D011188:Potassium; D005998:Glycine