Postsynaptic block of frog neuromuscular transmission by conotoxin GI.
Conotoxin GI, a peptide neurotoxin contained in the venom of the marine snail Conus geographus, was applied to the cutaneous pectoris muscle of the frog, and the effects on the postsynaptic response to acetylcholine were examined. Conotoxin GI reversibly blocked nerve-evoked muscle contractions at concentrations greater than or equal to 3 to 4 microM. Micromolar concentrations of conotoxin GI significantly reduced the amplitude of miniature endplate potentials and membrane depolarizations produced by ionophoretic application of acetylcholine, suggesting that the toxin reduced the postsynaptic sensitivity to acetylcholine. The reduction in the sensitivity of the muscle to acetylcholine was not due to changes in muscle fiber resting membrane potential or input resistance. Conotoxin GI reduced the amplitudes but did not affect the rates of decay of focal, extracellularly recorded endplate currents or miniature endplate currents, suggesting that the toxin did not affect the lifetime of ion channels opened by acetylcholine. Miniature endplate currents decay five to six times more slowly than normal when acetylcholinesterase is blocked with neostigmine methyl sulfate due to repeated binding of acetylcholine to receptors as it diffuses from the synaptic cleft. Conotoxin GI reduced the amplitude and increased the rate of decay of miniature endplate currents recorded in the presence of neostigmine methyl sulfate, suggesting that the toxin reduced the binding of acetylcholine to endplate receptors. These results are consistent with the hypothesis that conotoxin GI blocks neuromuscular transmission at the frog endplate by reducing the binding of acetylcholine to receptors.
McManus
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Musick
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D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002800:Cholinesterase Inhibitors; D020916:Conotoxins; D004594:Electrophysiology; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D008978:Mollusk Venoms / Q000494:pharmacology*; D009045:Motor Endplate / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects; D009132:Muscles / Q000294:innervation / Q000502:physiology; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology*; D011894:Rana pipiens; D013569:Synapses / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects*
D002800:Cholinesterase Inhibitors; D020916:Conotoxins; D008978:Mollusk Venoms; C029960:conotoxin GI; D000109:Acetylcholine