The experiments on isolated nerve fibers from the frog Rana ridibunda have demonstrated that aminoacridine tacrin and aminocholine amiridine given in a concentration of 1 microM induced a 3-4 mV increase in the resting potential of the intact Ranvier nodal membrane depolarized by several millivolts by external source current, accompanied by a rise in the amplitude and curvature of action potential. With the voltage clamp, the two agents shifted a steady state potassium conductivity vs. the voltage curve measured in the vicinity of the resting potential in isotonic KCl solution. The shift had a hyperpolarizing direction and magnitude of 1-2 mV at the agents' concentrations of 0.01-0.1 microM and 10 mV at concentrations higher than 1 microM. The resting potential change calculated on the basis of conductivity measurements was in agreement with that observed experimentally. It is suggested that the tacrin- and amiridine-induced shift of the voltage sensitivity region of potassium channels near the resting potential might underlie their therapeutic effects in patients with senile dementia of the Alzheimer type.

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