Are postsynaptic nicotinic end-plate receptors involved in lead toxicity?
The effects of Pb2+ on the postsynaptic nicotinic end-plate receptor were examined in the perfused mouse hemidiaphragm preparation. Postsynaptic nicotinic responses, evoked by pressure ejection of ACh, were blocked by Pb2+ in a transient way. After 9-12 min of exposure to 1 microM Pb2+ the amplitude of the depolarization induced by 1 mM ACh was reduced to 39.5 +/- 11% of the control value. During continued exposure to Pb2+ this blocking effect was reversed and after 30 min of exposure to 1 microM Pb2+ the amplitude of the ACh-induced depolarization had returned to the control value. The amplitude and the frequency of miniature end-plate potentials were not altered in the presence of 1 microM Pb2+. Under voltage clamp conditions the effects of Pb2+ on the ACh-induced inward current were similar to those of Pb2+ on the ACh-induced depolarization. After 12 min of exposure to 1 microM Pb2+ the inward current induced by 1 mM ACh was reduced to 44% of the control value and after 30 min the ACh-induced inward current had recovered to 94% of the control value. It is concluded that, in addition to the generally established mechanism of action of Pb2+ at the muscle end-plate, Pb2+ blocks the postsynaptic nicotinic receptor-mediated response at a relative low concentration. The contribution of these postsynaptic effects to the neurotoxic symptoms of Pb2+ remains to be established.
Oortgiesen
M
M
Department of Pharmacology, School of Medicine, University of Nevada, Reno 89557-0046.
Lewis
B K
BK
Bierkamper
G G
GG
Vijverberg
H P
HP
D000109:Acetylcholine; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D007854:Lead / Q000633:toxicity*; D008297:Male; D051379:Mice; D009045:Motor Endplate / Q000187:drug effects*; D009469:Neuromuscular Junction / Q000187:drug effects*; D011978:Receptors, Nicotinic / Q000187:drug effects*
D011978:Receptors, Nicotinic; D007854:Lead; D000109:Acetylcholine