The action of thiamine and its di- and triphosphates on the slow exponential decline of the ionic currents in the node of Ranvier

Abstract

Sodium and potassium currents in the node of Ranvier decrease exponentially with time during long lasting voltage clamp experiments. This decline is strongly dependent on temperature (Q 10 approximately 3). Thiamine and, particularly, its di- and triphosphoric acid esters are shown to prevent this exponential decline of the ionic currents. Thiamine acts from the outside and from the inside of the nodal membrane, but more potently from the inside. Thiamine diphosphate prevents the exponential decline of the ionic currents only when applied internally. Thiamine triphosphate, the most effective thiamine derivative was tested from the inside only. Bacterial thiaminases applied externally were not effective, presumably because they do not permeate the nodal membrane. Tetrodotoxin, that has been shown by other investigators to induce a release of thiamine from nerve membranes, does not alter the action of thiamine on the exponential decline of currents and vice versa. It is concluded that: (1) thiamine diphosphate or thiamine triphosphate are the active thiamine compounds in nerve membranes; (2) the site of action is located at the internal surface of the membrane; (3) the reduction of the thiamine concentration in the membrane or in the axoplasm could cause the exponential decline of currents; (4) the release of thiamine from nerve membranes induced by tetrodotoxin is interpreted as a side effect not even related to the mechanism by which tetrodotoxin blocks the sodium channels; (5) thiamine polyphosphates appear to stabilise the intrinsic electric field strength of the nodal membrane in the resting state. Therefore, as a working hypothesis, it is suggested that the thiamine derivatives control the number of functioning ionic channels by stabilising the density of negative surface charges at the inner side of the nerve membrane.