Novel variants of voltage-operated calcium channel α1-subunit transcripts in a rat liver-derived cell line: deletion in the IVS4 voltage sensing region

Brereton, Helen M.; Harland, M. Lyn; Froscio, Mario; Petronijevic, T.; Barritt, Greg J.

doi:10.1016/s0143-4160(97)90088-9

Cited by 40 publications

(31 citation statements)

References 40 publications

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“…Therefore we sought to identify whether authentic L-type channels, or L-type-related channels were expressed in T lymphocytes. Previous studies have identified transcripts for the L-type ␣ 1 1.1-, ␣ 1 1.2-, and ␣ 1 1.4-subunits in Jurkat T cells (28,29). We have previously demonstrated that human B lymphocytes express ␣ 1 1.2 transcripts and protein (26).…”

Section: L-type Ca 2ϩ Channel Antagonists Partially Inhibit Thapsigarmentioning

confidence: 74%

Non-voltage-gated L-type Ca2+ Channels in Human T Cells

Stokes¹,

Gordon²,

Grafton

2004

Journal of Biological Chemistry

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In T lymphocytes, engagement of the antigen receptor leads to a biphasic Ca 2؉ flux consisting of a mobilization of Ca 2؉ from intracellular stores followed by a lower but sustained elevation that is dependent on extracellular Ca 2؉ . The prolonged Ca 2؉ flux is required for activation of transcription factors and for subsequent activation of the T cell. Ca 2؉ influx requires as yet unidentified Ca 2؉ channels, which potentially play a role in T cell activation. Here we present evidence that human T cells express a non-voltage-gated Ca 2؉ channel related to L-type voltage-gated Ca 2؉ channels. Drugs that block classical L-type channels inhibited the initial phase of the antigen receptor-induced Ca 2؉ flux and could also inhibit the sustained phase of the Ca 2؉ signal suggesting a role for the L-type Ca 2؉ channel in antigen receptor signaling. T cells expressed transcripts for the ␣ 1 1.2 and ␣ 1 1.3 pore-forming subunits of L-type voltage-gated Ca 2؉ channels and transcripts for all four known ␤-subunits including several potential new splice variants. Jurkat T leukemia cells expressed a small amount of full-length ␣ 1 1.2 protein but the dominant form was a truncated protein identical in size to a truncated ␣ 1 1.2 protein known to be expressed in B lymphocytes. They further expressed a truncated form of the ␣ 1 1.3 subunit and auxiliary ␤1-and ␤3-subunit proteins. Our data strongly suggest that functional but non-voltage-gated L-type Ca 2؉ channels are expressed at the plasma membrane in T cells and play a role in the antigen receptor-mediated Ca 2؉ flux in these cells.

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Section: L-type Ca 2ϩ Channel Antagonists Partially Inhibit Thapsigarmentioning

confidence: 74%

Non-voltage-gated L-type Ca2+ Channels in Human T Cells

Stokes¹,

Gordon²,

Grafton

2004

Journal of Biological Chemistry

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“…Indeed, hepatocytes contain Ca 2ϩ channels that are mainly receptor activated but may also include voltageactivated Ca 2ϩ channels (Sawanobori et al, 1989;Brereton et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

A Calcium Flux Is Required for Circadian Rhythm Generation in Mammalian Pacemaker Neurons

Lundkvist¹,

Kwak²,

Davis³

et al. 2005

J. Neurosci.

166

163

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], reversibly abolished the rhythmic expression of Per1. In addition, the amplitude of Per1 expression was markedly decreased by voltage-gated Ca 2ϩ channel antagonists. A similar result was observed for mouse Per1 and PER2. Together, these results strongly suggest that a transmembrane Ca 2ϩ flux is necessary for sustained molecular rhythmicity in the SCN. We propose that periodic Ca 2ϩ influx, resulting from circadian variations in membrane potential, is a critical process for circadian pacemaker function.

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“…This "voltage-operable" current had different electrophysiological properties than I CRAC , but was activated through the TCR/CD3 complex and Ca 2ϩ store depletion (19,20). RT-PCR analysis has also shown that transcripts of the poreforming ␣ 1C -and ␣ 1S -subunits of L-type VDCCs are expressed in Jurkat T cells (21). In addition, Savignac et al (22) (23) demonstrated that 0.001-100 M nifedipine prevented the proliferation of human T lymphocytes in response to the mitogens, phytohemagglutinin (PHA), and concanavalin A (ConA).…”

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confidence: 99%

Identification and Functional Characterization of Voltage-dependent Calcium Channels in T Lymphocytes

Kotturi¹,

Carlow²,

Lee³

et al. 2003

Journal of Biological Chemistry

101

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In T lymphocytes, sustained calcium (Ca 2؉ ) influx through Ca 2؉ channels localized in the plasma membrane is critical for T cell activation and proliferation. Previous studies indicated that voltage-dependent Ca 2؉ channels (VDCCs) play a role in Ca 2؉ mobilization during T lymphocyte activation. However, the role of VDCCs in otherwise nonexcitable cells is still poorly understood. We used RT-PCR to identify a transcript encoding the pore-forming ␣ 1F -subunit of an L-type Ca 2؉ channel in T lymphocytes. Its identity was confirmed by DNA sequencing. To further investigate the contribution of Ca 2؉ influx through VDCCs, we assessed the effects of the 1,4-dihydropyridine L-type Ca 2؉ channel agonist, (؉/؊) Bay K 8644, and antagonist, nifedipine, on the human Jurkat T cell leukemia line, human peripheral blood T lymphocytes and mouse splenocytes. We found that treatment of T lymphocytes with (؉/؊) Bay K 8644 increased intracellular Ca 2؉ and induced the activation of phosphoextracellular-regulated kinase 1/2 (Erk1/2), whereas nifedipine blocked Ca 2؉ influx, the activity of Erk1/2 and nuclear factor of activated T cells (NFAT), interleukin-2 (IL-2) production, and IL-2 receptor expression. Nifedipine also significantly suppressed splenocyte proliferation in an in vitro mixed lymphocyte reaction and the proliferation of male antigen (H-Y)-specific T cell receptor-transgenic CD8 ؉ T cells in transplanted male mice in vivo. Taken together these novel findings indicate that an L-type Ca 2؉ channel plays a significant role in the Ca 2؉ influx pathways mediating T lymphocyte activation and proliferation in vitro and in vivo.

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Novel variants of voltage-operated calcium channel α1-subunit transcripts in a rat liver-derived cell line: deletion in the IVS4 voltage sensing region

Cited by 40 publications

References 40 publications

Non-voltage-gated L-type Ca2+ Channels in Human T Cells

Non-voltage-gated L-type Ca2+ Channels in Human T Cells

A Calcium Flux Is Required for Circadian Rhythm Generation in Mammalian Pacemaker Neurons

Identification and Functional Characterization of Voltage-dependent Calcium Channels in T Lymphocytes

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