Abstract
Depolarization of muscle end plates by carbamylcholine was reduced by 35-64% in muscles that had been treated with batrachotoxin or veratridine. Tetrodotoxin was used to prevent or reverse the membrane depolarization elicited by batrachotoxin or veratridine in the surface fibers of muscles, prior to the addition of carbamylcholine. But even when tetrodotoxin was added initially to prevent any depolarization of the muscle membrane by batrachotoxin, the latter toxin retained its inhibitory effect on the carbamylcholine response. Treatment with tetrodotoxin alone or tityustoxin followed by tetrodotoxin had no effect on the end plate depolarization induced by carbamylcholine. The inhibitory effect of veratridine on the response to carbamylcholine, but not that of batrachotoxin, was reversible. Prior treatment with batrachotoxin reduced responses to a bath-applied combination of acetylcholine plus neostigmine as well, while having no effect on responses to microiontophoretically applied acetylcholine, on miniature end plate potentials, or on end plate currents. The muscle depolarization elicited by batrachotoxin was unaffected by α-bungarotoxin, an acetylcholine receptor antagonist, or by histrionicotoxin, an antagonist of the ion conductance modulator associated with the acetylcholine receptor. The ability of batrachotoxin to alter the end plate response to carbamylcholine was found to be noncompetitive. The results are consonant with activation of tetrodotoxin-insensitive sodium channels by batrachotoxin and veratridine and the subsequent lack of participation of these activated channels in the depolarization of end plates by carbamylcholine. The depolarization elicited by carbamylcholine in a batrachotoxin-treated preparation thus reflects only the activation of acetylcholine receptor-ion conductance modulator complexes.
ACKNOWLEDGMENTS The authors express their appreciation to Miss Mabel Alice Zelle for excellent computer assistance and Mrs. Maria Luisa Diniz de Oliveira for secretarial assistance.
- Copyright © 1978 by Academic Press, Inc.
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