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(+)-Tubocurarine (TC) decreases the probability that the protozoan, Stentor coeruleus Ehrenberg, will contract in response to mechanical stimulation, because it selectively depresses mechanoreceptor currents. Resting membrane properties and action potentials are not significantly altered by the drug. Stentor incubated in media containing radioactively labelled TC (TC*) retain TC* after extensive washing despite a rather high apparent KD (19.7 mumol l-1). The incubation curve for TC* binding exhibits an initial exponential rise followed by a linear increase. Wash-out of bound TC* and elimination of the exponential component of the incubation curve is observed if the TC* incubation is followed by a 5-s exposure to 8% urea; therefore, the exponential component represents a reversible binding process. TC* binding in the exponential component is highly correlated (r less than −0.96) with the depression in receptor current and response probability when incubation time, drug concentration and drug (gallamine, TC, decamethonium and succinylcholine) are varied. These correlations suggest that the exponential binding is to functional mechanoreceptors. Mechanoreceptor currents are decreased by hyperpolarization and increased by depolarization, indicating that the mechanoreceptor channel is voltage-dependent. At hyperpolarized potentials the channels are in a form (the U form) which cannot be opened by mechanical stimulation; at depolarized potentials they are in a form (the R form) which can be opened. TC appears to bind to the U form with higher affinity than to the R form, since depolarization reduces the amount of bound TC* and relieves the depression of mechanoreceptor current produced by TC.

The Mechanism of Tubocurarine Action on Mechanoreceptor Channels in the Protozoan Stentor Coeruleus