Veratridine blocks voltage-gated potassium current in human T lymphocytes and in mouse neuroblastoma cells

(i) Effects of veratridine on ionic conductances of human peripheral blood T lymphocytes have been investigated using the whole-cell patch-clamp technique. (ii) Veratridine reduces the net outward current evoked by membrane depolarizations. The reduction originates from block of a 4-aminopyridine-sensitive, voltage-gated K+ current. (iii) Human T lymphocytes do not appear to express voltage-gated Na+ channels, since inward currents are observed neither in control nor in veratridine- and bretylium-exposed lymphocytes. (iv) The effect of veratridine consists of an increase in the rate of decay of the voltage-gated K+ current and a reduction of the peak current amplitude. Both effects depend on veratridine concentration. Half-maximum block occurs at 97 microM and the time constant of decay is reduced by 50% at 54 microM of veratridine. (v) Possible mechanisms of veratridine action are discussed. The increased rate of K+ current decay is most likely due to open channel block. The decrease of current amplitude may involve an additional mechanism. (vi) In cultured mouse neuroblastoma N1E-115 cells, veratridine blocks a component of voltage-gated K+ current, in addition to its effect on voltage-gated Na+ current. This result shows that the novel effect of veratridine is not confined to lymphocytes.