The ion channel of muscle and electric organ acetylcholine receptors: Differing affinities for noncompetitive inhibitors

Summary

• 1. Muscle and electric organ acetylcholine receptors (AChR's) were expressed inXenopus laevis oocytes and differential effects of noncompetitive blockers on each type of receptor were analyzed using a two-electrode voltage clamp.

• 2. The positively charged channel blockers, phencyclidine (PCP) and tetracaine, displayed a much lower potency on muscle receptor than on the electric organ receptor. The IC₅₀ for both blockers at the elecgrocyte receptor was close to 1µM at -60 mV and even lower at more hyperpolarized voltages. In contrast, with muscle receptor IC₅₀'s were 20 to 40µM at -60 or -80 mV.

• 3. Eupalmerin acetate, an uncharged noncompetitive inhibitor that displaces [³H]PCP from its high-affinity binding site, inhibited both receptors with a similar potency: IC₅₀ of 4.9 and 6.4µM for electrocyte and muscle receptors, respectively. However, eupalmerin acetate affected the desensitization process in each receptor type differently and triggered an unusual biphasic response in the muscle receptor.

• 4. These results are discussed with respect to differences in the amino acid sequences of the M2 regions of the two receptors.

• 5. A third type of noncompetitive inhibitor, Mg²⁺, was also examined and it inhibited both receptors with a similar potency (IC₅₀, 0.5-1.0 mM). However, Mg²⁺ appeared to act at sites other than the PCP site.