Actions of lead on transmitter release at mouse motor nerve terminals.
The actions of lead (Pb2+) on transmitter release were studied at neuromuscular junctions in mouse diaphragm in vitro. The quantal content of end-plate potentials (EPPs) was reduced by Pb2+ in a dose-related manner consistent with inhibition of Ca2+ entry into nerve terminals, with a half-maximal effect at 1.4 microM (in 0.5 mM Ca2+ and 2 mM Mg2+). Pb2+ also inhibited the increased frequency of MEPPs (fMEPP where MEPPs denotes miniature EPPs) produced by Ba2+ in the presence of raised K+, blocking the calculated Ba2+ entry half-maximally at 170 microM. However, at concentrations of 50-200 nM, Pb2+ often increased fMEPP in 20 mM K+ in the presence of Ca2+ and acted to promote the irreversible effect of lanthanum (La3+) to raise fMEPP. In nominally Ca(2+)-free solution with 20 mM K+, brief (1 min) application of Pb2+ (20-320 microM) caused rapid dose-dependent reversible rises in fMEPP. With prolonged exposure to Pb2+, fMEPP rose and then slowly declined; after removal of Pb2+, once fMEPP had fallen to low levels, fMEPP responded nearly normally to Ca2+ or ethanol, but not to Pb2+ itself. In 5 mM K+, 0 mM Ca2+ and varied [Pb2+] (where [] denotes concentration), nerve stimulation caused no EPPs, but prolonged tetanic stimulation produced increases in fMEPP graded with [Pb2+] that persisted as a "tail"; results were consistent with growth of fMEPP with the 4th power of intracellular Pb2+ and removal of intracellular Pb2+ with a time constant of about 30 s.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pharmacology and Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
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Wang
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Quastel
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D004558:Electric Stimulation; D004594:Electrophysiology; D007854:Lead / Q000494:pharmacology*; D051379:Mice; D009045:Motor Endplate / Q000502:physiology; D009411:Nerve Endings / Q000378:metabolism*; D009469:Neuromuscular Junction / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology
D018377:Neurotransmitter Agents; D007854:Lead; D011188:Potassium; D002118:Calcium