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.
Verheugen
J A
JA
Research Institute of Toxicology, Utrecht University, The Netherlands.
Oortgiesen
M
M
Vijverberg
H P
HP
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D002104:Cadmium / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004594:Electrophysiology; D006801:Humans; D066298:In Vitro Techniques; D008564:Membrane Potentials; D051379:Mice; D009447:Neuroblastoma / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D014701:Veratridine / Q000008:administration & dosage / Q000494:pharmacology*
D015221:Potassium Channels; D002104:Cadmium; D014701:Veratridine; D015761:4-Aminopyridine; D011188:Potassium