Charybdotoxin Inhibits Proliferation and Interleukin 2 Production in Human Peripheral Blood Lymphocytes

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1989 Dec 1

PMID 2481312

Citations 48

Authors

M Price

S C Lee

C Deutsch

Affiliations

Soon will be listed here.

Abstract

We demonstrate that blockade of the lymphocyte voltage-gated K+ channel by charybdotoxin (CTX) inhibits lymphocyte mitogenesis. Charybdotoxin blocks conductance with a Ki of 0.3 nM and inhibits mitogen- and antigen-stimulated proliferation with a Ki of 0.5 nM. As opposed to the other blockers of the lymphocyte K+ channel, the inhibition of mitogenesis by CTX can be overcome selectively by exogenous recombinant interleukin 2 (IL-2); endogenous levels of IL-2 in the culture supernatants of stimulated cells are decreased by the presence of CTX. Our results suggest that the voltage-gated K+ channel is either directly or indirectly involved in IL-2 synthesis and/or secretion.

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References

Matteson D, Deutsch C . K channels in T lymphocytes: a patch clamp study using monoclonal antibody adhesion. Nature. 1984; 307(5950):468-71. DOI: 10.1038/307468a0. View

Rink T, Montecucco C, Hesketh T, Tsien R . Lymphocyte membrane potential assessed with fluorescent probes. Biochim Biophys Acta. 1980; 595(1):15-30. DOI: 10.1016/0005-2736(80)90243-6. View

Gelfand E, Cheung R, Grinstein S . Role of membrane potential in the regulation of lectin-induced calcium uptake. J Cell Physiol. 1984; 121(3):533-9. DOI: 10.1002/jcp.1041210312. View

Mills G, Cheung R, Grinstein S, Gelfand E . Increase in cytosolic free calcium concentration is an intracellular messenger for the production of interleukin 2 but not for expression of the interleukin 2 receptor. J Immunol. 1985; 134(3):1640-3. View

Miller C, Moczydlowski E, Latorre R, Phillips M . Charybdotoxin, a protein inhibitor of single Ca2+-activated K+ channels from mammalian skeletal muscle. Nature. 1985; 313(6000):316-8. DOI: 10.1038/313316a0. View

Oettgen H, Terhorst C, Cantley L, Rosoff P . Stimulation of the T3-T cell receptor complex induces a membrane-potential-sensitive calcium influx. Cell. 1985; 40(3):583-90. DOI: 10.1016/0092-8674(85)90206-5. View

Sands S, Lewis R, Cahalan M . Charybdotoxin blocks voltage-gated K+ channels in human and murine T lymphocytes. J Gen Physiol. 1989; 93(6):1061-74. PMC: 2216250. DOI: 10.1085/jgp.93.6.1061. View

Smith K . Interleukin 2. Annu Rev Immunol. 1984; 2:319-33. DOI: 10.1146/annurev.iy.02.040184.001535. View

Gallin E . Ionic channels in leukocytes. J Leukoc Biol. 1986; 39(3):241-54. DOI: 10.1002/jlb.39.3.241. View

10.

Lee S, Sabath D, Deutsch C, Prystowsky M . Increased voltage-gated potassium conductance during interleukin 2-stimulated proliferation of a mouse helper T lymphocyte clone. J Cell Biol. 1986; 102(4):1200-8. PMC: 2114188. DOI: 10.1083/jcb.102.4.1200. View

11.

Greene W, Leonard W . The human interleukin-2 receptor. Annu Rev Immunol. 1986; 4:69-95. DOI: 10.1146/annurev.iy.04.040186.000441. View

12.

Deutsch C, Krause D, Lee S . Voltage-gated potassium conductance in human T lymphocytes stimulated with phorbol ester. J Physiol. 1986; 372:405-23. PMC: 1192770. DOI: 10.1113/jphysiol.1986.sp016016. View

13.

Smith C, Phillips M, Miller C . Purification of charybdotoxin, a specific inhibitor of the high-conductance Ca2+-activated K+ channel. J Biol Chem. 1986; 261(31):14607-13. View

14.

DeCoursey T, Chandy K, Gupta S, Cahalan M . Mitogen induction of ion channels in murine T lymphocytes. J Gen Physiol. 1987; 89(3):405-20. PMC: 2215901. DOI: 10.1085/jgp.89.3.405. View

15.

Hermann A, Erxleben C . Charybdotoxin selectively blocks small Ca-activated K channels in Aplysia neurons. J Gen Physiol. 1987; 90(1):27-47. PMC: 2228863. DOI: 10.1085/jgp.90.1.27. View

16.

Lee S, Price M, Prystowsky M, Deutsch C . Volume response of quiescent and interleukin 2-stimulated T-lymphocytes to hypotonicity. Am J Physiol. 1988; 254(2 Pt 1):C286-96. DOI: 10.1152/ajpcell.1988.254.2.C286. View

17.

Gimenez-Gallego G, Navia M, Reuben J, KATZ G, Kaczorowski G, Garcia M . Purification, sequence, and model structure of charybdotoxin, a potent selective inhibitor of calcium-activated potassium channels. Proc Natl Acad Sci U S A. 1988; 85(10):3329-33. PMC: 280202. DOI: 10.1073/pnas.85.10.3329. View

18.

Mackinnon R, Miller C . Mechanism of charybdotoxin block of the high-conductance, Ca2+-activated K+ channel. J Gen Physiol. 1988; 91(3):335-49. PMC: 2216138. DOI: 10.1085/jgp.91.3.335. View

19.

Modiano J, Kelepouris E, Kern J, Nowell P . Requirement for extracellular calcium or magnesium in mitogen-induced activation of human peripheral blood lymphocytes. J Cell Physiol. 1988; 135(3):451-8. DOI: 10.1002/jcp.1041350312. View

20.

Gardner P, Alcover A, Kuno M, Moingeon P, Weyand C, Goronzy J . Triggering of T-lymphocytes via either T3-Ti or T11 surface structures opens a voltage-insensitive plasma membrane calcium-permeable channel: requirement for interleukin-2 gene function. J Biol Chem. 1989; 264(2):1068-76. View