Showing papers by "Edson X. Albuquerque published in 1973"

Acetylcholine Receptor and Ion Conductance Modulator Sites at the Murine Neuromuscular Junction: Evidence from Specific Toxin Reactions

Abstract: The perhydro derivative of histrionicotoxin reversibly blocks the excitatory ionic transduction system in the synaptic and sarcolemmal membranes of mammalian skeletal muscle cells. The efficacy of perhydrohistrionicotoxin as an antagonist at the post-synaptic membrane is increased by the transient presence of acetylcholine in the endplate of innervated muscles and at extrajunctional receptors in denervated muscles. α-Bungarotoxin and [3H]monoacetyl-α-bungarotoxin block the endplate acetylcholine receptors, each binding to the same extent. The effect of bungarotoxin is partially reversible. These electrophysiological results, together with the effects of perhydrohistrionicotoxin and/or d-tubocurarine on the binding of [3H]monoacetyl-α-bungarotoxin at endplates of murine diaphragm muscle and on the bungarotoxin-elicited irreversible blockade of neuromuscular transmission, suggest that at least two types of sites participate in the synaptic excitation by acetylcholine. One site, competitively blocked by bungarotoxin and by curare, is presumably the acetylcholine receptor. Binding of bungarotoxin at this site is responsible for an irreversible blockade of neuromuscular transmission. The second site, competitively blocked by bungarotoxin and perhydrohistrionicotoxin, is proposed to be part of the cholinergic ion conductance modulator. Binding of bungarotoxin to this site does not result in an irreversible blockade.

The pharmacology of batrachotoxin. V. A comparative study of membrane properties and the effect of batrachotoxin on sartorius muscles of the frogs Phyllobates aurotaenia and Rana pipiens.

Abstract: Membrane properties and the effects of batrachotoxin (BTX) and tetrodotoxin were studied on sartorius muscles of Rana pipiens and of Phyllobates aurotaenia , the frog which produces BTX. There was no significant difference in the resting membrane potential, amplitude and time course of miniature end-plate potentials or the quantum content recorded in sartorius muscles of the two frogs. The frequency of spontaneous transmitterrelease was, however, higher in the sartorius muscles of P. aurotaenia than in R. pipiens . Both the time constant and specific resistance of a unit area of membrane of the sartorius muscles of P. aurotaenia were significantly lower (P < .01) than those of R. pipiens muscle fibers. The intracellularly recorded action potential of sartorius muscles from both frogs was blocked by removal of the external sodium or by exposure to tetrodotoxin. BTX (1.2 x 10-6 M) had no effect on membrane potential, miniature end-plate potential amplitude and frequency, spike generation or twitch of the nerve-muscle preparations of P . aurolaenia . When sartorius muscles of R. pipiens were stimulated at a frequency of 0.2 puLse/sec and exposed to BTX (4.0 x 10-8 M), the indirectly elicited muscle twitch was blocked and all surface fibers were depolarized within 13 minutes: simultaneously, there was a transient muscle contracture lasting seven to eight minutes. Veratridine (7.5 x 10-6 M) depolarized the surface fibers of stimulated sartorius muscles from P. anrotaenia by 20 mV after one hour but those of R. pipiens were depolarized by 95 mV within 15 minutes. BTX-depolarized sartorius muscles of R. pipiens were insensitive to isotonic KCl, whereas caffeine (20 mM) induced a normal contracture. Electron microscopic obesrvations of BTX-treated sartorius muscles from R. pipiens revealed damage to only the presynaptic