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PMID: 1279670 Published · ppublish English Journal Article

Selective blockers of voltage-gated K+ channels depolarize human T lymphocytes: mechanism of the antiproliferative effect of charybdotoxin.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 89 ·No. 21 ·1992-11-01 ·Pages 10094-8

Leonard RJ, Garcia ML, Slaughter RS, Reuben JP

Abstract

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.

MeSH Terms
Calcium/pharmacology Cells, Cultured Charybdotoxin Egtazic Acid/pharmacology Electric Conductivity/drug effects Humans Ion Channel Gating/drug effects Kinetics Lymphocyte Activation/drug effects Membrane Potentials/drug effects Neurotoxins/pharmacology Potassium Channels/drug effects,physiology Scorpion Venoms/pharmacology T-Lymphocytes/drug effects,immunology,physiology Time Factors
Chemicals
Neurotoxins Potassium Channels Scorpion Venoms Charybdotoxin Egtazic Acid margatoxin noxiustoxin Calcium
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Leonard R J
Department of Membrane Biochemistry and Biophysics, Merck Research Laboratories, Rahway, NJ 07065.
Garcia M L
Slaughter R S
Reuben J P
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.89.21.10094
Published
1992-11-01
Pages
10094-8
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC50284
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.89.21.10094 PMC Full Text View journal details
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