Role for the skeletal muscle action potential in non-Hebbian long-term depression at the amphibian (Bufo marinus) neuromuscular junction.
Retrograde signaling from skeletal muscle cells to motor nerve terminals is a recognized mechanism for modulating the strength of neuromuscular transmission. We recently described a form of long-term depression of transmitter release at the mature neuromuscular junction that is dependent on the production of nitric oxide, most likely by the muscle cell (Etherington and Everett 2004 J Physiol (Lond) 559:507-517). We now show that the depression is blocked by treating neuromuscular preparations with mu-conotoxin G111A, an antagonist of skeletal muscle voltage gated sodium channels, indicating that the depression requires postsynaptic action potential firing. Experiments on dually-innervated sartorius muscles revealed that propagation of action potentials generated by low-frequency stimulation of one nerve branch gives rise to nitric-oxide mediated depression at unstimulated nerve terminals located many millimetres away on the same muscle fiber. The non-Hebbian pattern of expression of the depression, as well as its reliance on postsynaptic action potential firing, distinguish it from forms of synaptic depression described at immature neuromuscular synapses and may provide a mechanism for coregulation of the strength of motoneurons innervating the same postsynaptic cell.
Etherington
Sarah Jane
SJ
School of Biomedical, Biomolecular and Chemical Sciences, The University of Western Australia, Crawley 6009, Australia.
Everett
Alan William
AW
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D002024:Bufo marinus; D020916:Conotoxins / Q000494:pharmacology; D019054:Evoked Potentials, Motor / Q000502:physiology; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology*; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology
D020916:Conotoxins; C046101:conotoxin GIII; D009569:Nitric Oxide