THE ION-CHANNEL OF MUSCLE AND ELECTRIC ORGAN ACETYLCHOLINE-RECEPTORS - DIFFERING AFFINITIES FOR NONCOMPETITIVE INHIBITORS

1. Muscle and electric organ acetylcholine receptors (AChR's) were exp ressed in Xenopus laevis oocytes and differential effects of noncompet itive blockers on each type of receptor were analyzed using a two-elec trode voltage clamp. 2. The positively charged channel blockers, phenc yclidine (PCP) and tetracaine, displayed a much lower potency on muscl e receptor than on the electric organ receptor. The IC50 for both bloc kers at the elecgrocyte receptor was close to 1 muM at -60 mV and even lower at more hyperpolarized voltages. In contrast, with muscle recep tor IC50's were 20 to 40 muM at -60 or -80 mV. 3. Eupalmerin acetate, an uncharged noncompetitive inhibitor that displaces [H-3]PCP from its high-affinity binding site, inhibited both receptors with a similar p otency: IC50 of 4.9 and 6.4 muM for electrocyte and muscle receptors, respectively. However, eupalmerin acetate affected the desensitization process in each receptor type differently and triggered an unusual bi phasic response in the muscle receptor. 4. These results are discussed with respect to differences in the amino acid sequences of the M2 reg ions of the two receptors. 5. A third type of noncompetitive inhibitor , Mg2+, was also examined and it inhibited both receptors with a simil ar potency (IC50, 0.5-1.0 mM). However, Mg2+ appeared to act at sites other than the PCP site.