Action of lipid-soluble quaternary ammonium ions on the resting potential of myelinated nerve fibers of the frog
Biochimica et Biophysica Acta 32: 381-386
ISSN/ISBN: 0006-3002 PMID: 13816234 DOI: 10.1016/0006-3002(59)90610-9
This paper presents an approach to the mechanism of action of lipid-soluble quaternary ammonium ions (PAD (pyridine-2-aldoxime dodeciodide), PDI (pyridine dodeciodide), noracetylcholine 12) by analyzing their effect on the resting potential of nerve fibers. The degree of depolarization depends on the concentration of the compounds. The time course is slower than with 2 x 10-2 M KC1. PAD is the most effective of the 3 compounds investigated. Washing with Ringer's solution brings the potential back to the initial value after 30 min (10-4M PAD, 5 x 10-4 M noracetylcholine). When smaller concentrations of PAD are used, the depolarization is reversed in a shorter time. The depolarization must be the result of a change in the relative permeability of the various active ions. Physostigmine-Ringer's solution scarcely alters the resting potential. Physostigmine (7 x 10-3 M) inhibits the depolarization of 10-4 M PAD. Lower concentrations of physostigmine counteract the effect of PAD, but do not abolish it, while higher concentrations of PAD overcome the protective action. The antagonism between PAD and physostigmine is typical for competitive agents. It is suggested that the lipid-soluble quaternary ammonium ions act with a receptor and that this reaction effects a change in permeability.