Selective blockers of voltage-gated K+ channels depolarize human T lymphocytes: mechanism of the antiproliferative effect of charybdotoxin.
Charybdotoxin (ChTX), a K+ channel blocker, depolarizes human peripheral T lymphocytes and renders them insensitive to activation by mitogen. We observed four types of K+ channels in human T cells: one voltage-activated, and three Ca(2+)-activated. To discern the mechanism by which ChTX depolarizes T cells, we examined the sensitivity of both the voltage-activated and Ca(2+)-activated K+ channels to ChTX and other peptide channel blockers. All four types were blocked by ChTX, whereas noxiustoxin and margatoxin blocked only the voltage-activated channels. All three toxins, however, produced equivalent depolarization in human T cells. We conclude that the membrane potential of resting T cells is set by voltage-activated channels and that blockade of these channels is sufficient to depolarize resting human T cells and prevent activation.
D002118:Calcium / Q000494:pharmacology; D002478:Cells, Cultured; D018999:Charybdotoxin; D004533:Egtazic Acid / Q000494:pharmacology; D004553:Electric Conductivity / Q000187:drug effects; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects; D007700:Kinetics; D008213:Lymphocyte Activation / Q000187:drug effects*; D008564:Membrane Potentials / Q000187:drug effects; D009498:Neurotoxins / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D012604:Scorpion Venoms / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D013997:Time Factors
D009498:Neurotoxins; D015221:Potassium Channels; D012604:Scorpion Venoms; D018999:Charybdotoxin; D004533:Egtazic Acid; C077910:margatoxin; C052567:noxiustoxin; D002118:Calcium