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Selective blockers of voltage-gated K+ channels depolarize human T lymphocytes: mechanism of the antiproliferative effect of charybdotoxin.
Open accessAbstract
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.
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Hamill, O. P., Marty, A., Neher, E., Sakmann, B., & Sigworth, F. J. (1981) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/bf00656997 · Cited by 18,436
Price, M., Lee, S. C., & Deutsch, C. (1989) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.86.24.10171 · Cited by 183
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Calcium signaling mechanisms in T lymphocytes.
Lewis, R. S. (2001) · Annual Review of Immunology · doi:10.1146/annurev.immunol.19.1.497 · Cited by 860
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Cahalan, M. D., & Chandy, K. G. (2009) · Immunological Reviews · doi:10.1111/j.1600-065x.2009.00816.x · Cited by 599
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Feske, S., Skolnik, E. Y., & Prakriya, M. (2012) · Nature Reviews Immunology · doi:10.1038/nri3233 · Cited by 441
Garcia-Calvo, M., Leonard, R. J., Novick, J., Stevens, S. P., Schmalhofer, W., Kaczorowski, G. J., & Garcia, M. L. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)46707-x · Cited by 345
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Metadata
- Authors
- Leonard, R. J., Garcia, M. L., Slaughter, R. S., & Reuben, J. P.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1992-11
- Volume
- 89
- Issue
- 21
- Pages
- 10094-10098
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2012462160
- Cited by
- 244
- References
- 2
- FWCI
- 4.07
- Type
- journal article
- Language
- en
- Open access
- green
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- Leonard, R. J., Garcia, M. L., Slaughter, R. S., & Reuben, J. P. (1992). 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. https://doi.org/10.1073/pnas.89.21.10094
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