Down-regulation of evoked synaptic release in rat neuromuscular junction.
Spontaneous and evoked synaptic transmission were studied at the rat extensor digitorum longus (EDL) neuromuscular junction in the presence of CGIIIA mu-conotoxin, a peptide which suppresses action potential in the sarcolemma, while not affecting impulse conduction along motor nerve fibers. The binomial parameters m (mean quantal content) and n (number of units involved in evoked quantal release) increased as a function of extracellular Ca++ ([Ca++]o), up to the physiological concentration (2 mM). Additional Ca++ failed to induce a statistically significant increase in either m or n, while the probability of activation (p) did increase, approaching unity at 4 mM [Ca++]o. In cut EDL preparations, without CGIIIA, the relation between end-plate potential amplitude and [Ca++]o resembled that for quantal content in unlesioned, CGIIIA-treated muscles. In contrast, normal preparations exposed to 0.5 mg/ml d-tubocurarine were much more responsive to Ca++ variations, with a significant end-plate potential amplitude increase in the presence of 4 mM [Ca++]o. However, in curarized preparation the evoked release was remarkably affected by repetitive stimulation, while in the absence of postsynaptic blockers release levels were more stable. We suggest that the stimulatory effect of extracellular Ca++ on evoked release at the mammalian neuromuscular junction might normally be depressed under physiological conditions, possibly by a down-regulation mechanism involving presynaptic nicotinic receptors. Such inhibition would increase nerve transmission efficiency during prolonged motor terminal activity.
Di Gregorio
F
F
Department of Peripheral Nervous System Research, FIDIA Research Laboratories, Abano Terme (PD), Italy.
Cereser
S
S
Favaro
G
G
Fiori
M G
MG
D000818:Animals; D002118:Calcium / Q000502:physiology; D020916:Conotoxins / Q000494:pharmacology; D003472:Curare / Q000494:pharmacology; D015536:Down-Regulation; D005110:Extracellular Space / Q000378:metabolism; D008297:Male; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology*; D003473:Neuromuscular Nondepolarizing Agents / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000502:physiology*
D020916:Conotoxins; D003473:Neuromuscular Nondepolarizing Agents; C046101:conotoxin GIII; D003472:Curare; D002118:Calcium