The action of the antituberculous agent ethambutol on the myelinated nerve was studied in two ways: (1) Resting and compound action potentials of the desheathed sciatic nerve were measured; (2) Na+ and K+ currents through the node of Ranvier were investigated by means of the voltage clamp. Reversible dose-dependent decreases of the compound action potential and of the conduction velocity were observed when ethambutol was applied in concentrations of 1--7 mM for 15 min; prolongation up to 60 min caused irreversible changes in membrane function and a decrease in Ca content. Ethambutol induced a hyperpolarizing change of the resting potential. When the nerve was depolarized in Ca2+-free solutions, ethambutol repolarized the nerve membrane. Ethambutol instantly reduced sodium and potassium currents through the nodal membrane. Presumably ethambutol acts primarily as a Ca2+ chelating cation on negative charges at the nerve membrane.
Action Potentials Animals