Decamethonium in depolarized muscle and the effects of tubocurarine

Abstract

1. In rat diaphragms immersed in solution containing 5 mM potassium the maximum uptake of labelled decamethonium was found at the end-plate region. In muscles depolarized in solution containing potassium methyl sulphate the uptake was reduced but a peak concentration at the end-plate region was still demonstrated.2. The uptake of labelled decamethonium increased steadily with time and was interpreted in terms of the entry of decamethonium into the fibres. The permeability at 10-100 muM was similar to that of sodium.3. The uptake of decamethonium at the end-plate region was dependent on the concentration. At low values the uptake in depolarized muscle was uniform along the fibres. Increase in concentration produced a peak at the end-plate region. This was interpreted as a change in permeability such that half the maximum effect was present at a concentration of approximately 5 muM.4. At high concentrations the influx showed saturation and carrier-like kinetics with a half-saturation concentration of 400 muM.5. Tubocurarine inhibited the peak uptake in depolarized diaphragm. The results were consistent with competitive inhibition with an inhibitory constant of 0.07 muM.6. Acetylcholine in high concentration also inhibited the uptake of decamethonium in the end-plate region of depolarized muscle.