INTERACTIONS OF D-TUBOCURARINE WITH THE NICOTINIC ACETYLCHOLINE-RECEPTOR CHANNEL MOLECULE

  • 1 January 1982
    • journal article
    • research article
    • Vol. 220  (1) , 172-177
Abstract
The interactions of d-tubocurarine (d-TC) with the ionic channel of the nicotinic acetylcholine receptor were studied by biochemical methods in Torpedo ocellata electric organ membranes and by electrophysiological methods on frog [Rana pipiens] sciatic nerve-sartorius muscle preparation. Torpedo membranes were treated with .alpha.-bungarotoxin to inhibit the acetylcholine receptor sites, then binding of [3H]perhydrohistrionicotoxin to the ionic channel sites was studied and was inhibited by d-TC. At 37.degree. C the Ki of d-TC was 10 .mu.M and at 22.degree. C it was 100 .mu.M. The affinity of d-TC for the ionic channel sites relative to that of perhydrohistrionicotoxin was constant at temperatures from 2-20.degree. C, but increased at higher temperatures up to 37.degree. C. The peak endplate current amplitude was depressed with 1-2 .mu.M d-TC in a voltage-dependent manner, with considerable departure from linearity at 10 and 30.degree. C. The effect of d-TC on spontaneous miniature endplate currents was similar and slightly more potent. The time constant of endplate current decay was decreased by d-TC (1 and 2 .mu.M) at temperatures of 10, 15 and 30.degree. C. The channel lifetime was reduced by d-TC, but channel conductance was unaffected. d-TC may interact with both the acetylcholine receptor sites as well as its ionic channel sites in closed and open conformations.