The DOI matches its Crossref record; 48 of the 48 references it cites were found in a registry or an index.
Up-regulation of the IKCa1 Potassium Channel during T-cell Activation
Open accessAbstract
We used whole cell recording to evaluate functional expression of the intermediate conductance Ca(2+)-activated K(+) channel, IKCa1, in response to various mitogenic stimuli. One to two days following engagement of T-cell receptors to trigger both PKC- and Ca(2+)-dependent events, IKCa1 expression increased from an average of 8 to 300-800 channels/cell. Selective stimulation of the PKC pathway resulted in equivalent up-regulation, whereas a calcium ionophore was relatively ineffective. Enhancement in IKCa1 mRNA levels paralleled the increased channel number. The genomic organization of IKCa1, SKCa2, and SKCa3 were defined, and IK(Ca) and SK(Ca) genes were found to have a remarkably similar intron-exon structure. Mitogens enhanced IKCa1 promoter activity proportional to the increase in IKCa1 mRNA, suggesting that transcriptional mechanisms underlie channel up-regulation. Mutation of motifs for AP1 and Ikaros-2 in the promoter abolished this induction. Selective Kv1.3 inhibitors ShK-Dap(22), margatoxin, and correolide suppressed mitogenesis of resting T-cells but not preactivated T-cells with up-regulated IKCa1 channel expression. Selectively blocking IKCa1 channels with clotrimazole or TRAM-34 suppressed mitogenesis of preactivated lymphocytes, whereas resting T-cells were less sensitive. Thus, Kv1.3 channels are essential for activation of quiescent cells, but signaling through the PKC pathway enhances expression of IKCa1 channels that are required for continued proliferation.
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Cites
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Self-citationA Component of Calcium-activated Potassium Channels Encoded by the Drosophila slo Locus
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Cited by
The functional network of ion channels in T lymphocytes
Cahalan, M. D., & Chandy, K. G. (2009) · Immunological Reviews · doi:10.1111/j.1600-065x.2009.00816.x · Cited by 599
Self-citationRole of membrane potential in the regulation of cell proliferation and differentiation
Sundelacruz, S., Levin, M., & Kaplan, D. L. (2009) · Stem Cell Reviews and Reports · doi:10.1007/s12015-009-9080-2 · Cited by 489
Ion channels and transporters in lymphocyte function and immunity
Feske, S., Skolnik, E. Y., & Prakriya, M. (2012) · Nature Reviews Immunology · doi:10.1038/nri3233 · Cited by 441
Levitan, I., Fang, Y., Rosenhouse-Dantsker, A., & Romanenko, V. (2010) · Subcellular Biochemistry · doi:10.1007/978-90-481-8622-8_19 · Cited by 247
Pedarzani, P., & Stocker, M. (2008) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-008-8216-x · Cited by 173
Metadata
- Authors
- Ghanshani, S., Wulff, H., Miller, M. J., Rohm, H., Neben, A., Gutman, G. A., Cahalan, M. D., & Chandy, K. G.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2000-11
- Volume
- 275
- Issue
- 47
- Pages
- 37137-37149
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2094401453
- Cited by
- 406
- References
- 48
- FWCI
- 5.07
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Ghanshani, S., Wulff, H., Miller, M. J., Rohm, H., Neben, A., Gutman, G. A., Cahalan, M. D., & Chandy, K. G. (2000). Up-regulation of the IKCa1 Potassium Channel during T-cell Activation. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m003941200
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