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

In T lymphocytes, sustained calcium (Ca2+) influx through Ca2+ channels localized in the plasma membrane is critical for T cell activation and proliferation. Previous studies indicated that voltage-dependent Ca2+ channels (VDCCs) play a role in Ca2+ 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 α1F-subunit of an L-type Ca2+ channel in T lymphocytes. Its identity was confirmed by DNA sequencing. To further investigate the contribution of Ca2+ influx through VDCCs, we assessed the effects of the 1,4-dihydropyridine L-type Ca2+ 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 Ca2+ and induced the activation of phosphoextracellular-regulated kinase 1/2 (Erk1/2), whereas nifedipine blocked Ca2+ 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 Ca2+ channel plays a significant role in the Ca2+ influx pathways mediating T lymphocyte activation and proliferation in vitro and in vivo. In T lymphocytes, sustained calcium (Ca2+) influx through Ca2+ channels localized in the plasma membrane is critical for T cell activation and proliferation. Previous studies indicated that voltage-dependent Ca2+ channels (VDCCs) play a role in Ca2+ 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 α1F-subunit of an L-type Ca2+ channel in T lymphocytes. Its identity was confirmed by DNA sequencing. To further investigate the contribution of Ca2+ influx through VDCCs, we assessed the effects of the 1,4-dihydropyridine L-type Ca2+ 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 Ca2+ and induced the activation of phosphoextracellular-regulated kinase 1/2 (Erk1/2), whereas nifedipine blocked Ca2+ 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 Ca2+ channel plays a significant role in the Ca2+ influx pathways mediating T lymphocyte activation and proliferation in vitro and in vivo. In T lymphocytes, calcium (Ca2+) plays a fundamental role as a second messenger in regulating numerous cellular functions, including activation, proliferation, and death (1Berridge M.J. Lipp P. Bootman M.D. Nat. Rev. Mol. Cell. Biol. 2000; 1: 11-21Crossref PubMed Scopus (4493) Google Scholar, 2Medema J.P. Borst J. Hum. Immunol. 1999; 60: 403-411Crossref PubMed Scopus (22) Google Scholar). The events surrounding Ca2+ mobilization in T lymphocytes are tightly regulated through membrane receptors, signaling molecules, and ion channels. Intracellular Ca2+ release is initiated through the recognition of antigen/major histocompatibility complex by the T cell receptor (TCR) 1The abbreviations used are: TCRT cell receptorIP3inositol 1,4,5-trisphosphateERendoplasmic reticulumNFATnuclear factor of activated T cellsIL-2interleukin-2IP3RIP3 receptorTRPtransient receptor potentialVDCCsvoltage-dependent Ca2+ channelsCRAC channelCa2+ release-activated Ca2+ channelICRACCRAC currentDHP1,4-dihydropyridinePHAphytohemagglutininConAconcanavalin APBMCsperipheral blood mononuclear cellsTgtransgenicmAbmonoclonal antibodyrhIL-2recombinant human IL-2PBTsperipheral blood T lymphocytesMAPmitogen-activated proteinErk1/2extracellular-regulated kinase1/2TPA12-O-tetradecanoylphorbol 13-acetateIL-2RIL-2 receptorPIpropidium iodideCFSE5-(and-6)-carboxyfluorescein diacetate, succinimidyl esterMLRmixed lymphocyte reactionKv channelsvoltage-dependent potassium channelsK+potassiumNTno treatment./CD3 complex during T lymphocyte activation (3van Leeuwen J.E. Samelson L.E. Curr. Opin. Immunol. 1999; 11: 242-248Crossref PubMed Scopus (217) Google Scholar). Following ligation of the TCR, non-receptor tyrosine kinases phosphorylate and activate phospholipase Cγ1, which cleaves phosphatidylinositol 4,5-bisphosphate from plasma membrane phospholipids to generate diacylglycerol and inositol 1,4,5-trisphosphate (IP3) (4Scharenberg A.M. Kinet J.P. Cell. 1998; 94: 5-8Abstract Full Text Full Text PDF PubMed Scopus (205) Google Scholar). Elevated levels of IP3 in the cytosol lead to the release of Ca2+ from intracellular stores in the endoplasmic reticulum (ER) and a sustained Ca2+ influx from the extracellular space (5Patel S. Joseph S.K. Thomas A.P. Cell Calcium. 1999; 25: 247-264Crossref PubMed Scopus (373) Google Scholar, 6Guse A.H. Crit. Rev. Immunol. 1998; 18: 419-448Crossref PubMed Google Scholar). A sustained Ca2+ signal ranging from a concentration of ∼200 nm to >1 μm for up to 48 h is necessary to activate nuclear factor of activated T cells (NFAT), a transcription factor that regulates the expression of various cytokine genes including interleukin-2 (IL-2) (7Lewis R.S. Annu. Rev. Immunol. 2001; 19: 497-521Crossref PubMed Scopus (707) Google Scholar). T cell receptor inositol 1,4,5-trisphosphate endoplasmic reticulum nuclear factor of activated T cells interleukin-2 IP3 receptor transient receptor potential voltage-dependent Ca2+ channels Ca2+ release-activated Ca2+ channel CRAC current 1,4-dihydropyridine phytohemagglutinin concanavalin A peripheral blood mononuclear cells transgenic monoclonal antibody recombinant human IL-2 peripheral blood T lymphocytes mitogen-activated protein extracellular-regulated kinase1/2 12-O-tetradecanoylphorbol 13-acetate IL-2 receptor propidium iodide 5-(and-6)-carboxyfluorescein diacetate, succinimidyl ester mixed lymphocyte reaction voltage-dependent potassium channels potassium no treatment. Although the mechanisms of Ca2+ release from the intracellular stores within T lymphocytes are well characterized, the Ca2+ entry pathway from extracellular sources into T lymphocytes still remains elusive despite the fact that it contributes to the majority of elevated intracellular Ca2+ during T lymphocyte activation (8Haverstick D.M. Engelhard V.H. J. Immunol. Google Scholar). for Ca2+ channels in the plasma membrane of T lymphocytes including IP3 receptor Ca2+ of transient receptor potential Ca2+ and L-type voltage-dependent Ca2+ channels that a plasma membrane Ca2+ to the found in the was for Ca2+ influx in T lymphocytes S. PubMed Scopus Google Scholar). A confirmed that T lymphocytes of the Ca2+ channel as plasma membrane J. Biol. 2000; Full Text Full Text PDF PubMed Google Scholar). However, the the of these channels to Ca2+ influx during T cell activation J. J. 1998; PubMed Scopus Google Scholar). on of T lymphocytes lead to a second for Ca2+ entry the plasma membrane through Ca2+ channels M.D. 1999; PubMed Scopus Google Scholar, M.D. J. Cell Biol. 2000; PubMed Scopus Google Scholar). Although the identity of the CRAC channel is still potential the of ion channels P. J. PubMed Scopus Google Scholar, J. J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar, S. 2001; PubMed Scopus Google Scholar). to the for the CRAC the to of the with CRAC current J. J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar, 2001; PubMed Scopus Google Scholar). is also to the of Ca2+ channels in the plasma membrane of T lymphocytes. VDCCs are are to in the potential the plasma membrane Rev. 1999; PubMed Google Scholar). The of the is that nonexcitable as T lymphocytes, a Ca2+ channel that with a of cells is by in membrane for the of Ca2+ channels in T lymphocytes PubMed Scopus (22) Google Scholar, D.M. J. PubMed Google an current in the plasma membrane of Jurkat T lymphocytes. current was activated through the complex and Ca2+ PubMed Scopus (22) Google Scholar, D.M. J. PubMed Google Scholar). also that of the pore-forming and of L-type VDCCs are in Jurkat T cells Cell Calcium. PubMed Scopus Google Scholar). In P. P. J. J. 2001; PubMed Scopus Google that T cell L-type Ca2+ channel and studies further to the expression of VDCCs in T lymphocytes. it that the 1,4-dihydropyridine L-type Ca2+ channel antagonist, nifedipine, is a of T lymphocyte proliferation. an in vitro J. Immunol. Google that μm nifedipine the proliferation of human T lymphocytes in to the phytohemagglutinin and concanavalin A In a human peripheral blood mononuclear cells with to in the of μm the of IL-2 the in the cells S. J. Immunol. PubMed Scopus Google Scholar). it through in vitro proliferation that nifedipine a on T lymphocyte proliferation in with the A Google Scholar, PubMed Scopus Google Scholar). The of was to the contribution of Ca2+ influx through VDCCs during T lymphocyte activation and proliferation. We by a to for the that the pore-forming α1F-subunit L-type Ca2+ channel transcript is in human T lymphocytes. the of a in T lymphocytes, we that L-type Ca2+ channels play a critical role in activation. We that (+/-) Bay K 8644 that L-type Ca2+ channel and nifedipine that L-type Ca2+ and signaling events during T lymphocyte activation and proliferation. The in the of a L-type in the plasma membrane of T lymphocytes. mice a transgenic receptor for the male antigen by and and mice in the of and used and of mice studies by the on the of the by the on Cell and human T cell leukemia Jurkat was from in with and and of T blood was from human male and by for a The was and in with and for h with monoclonal antibody and in recombinant human IL-2 for in the of the human peripheral blood T lymphocytes was on a with mouse and with the activated human with cells from in RT-PCR and DNA with an of from Jurkat T T and CD8+ T cells with the and used to and human and CD8+ T cells from human and human from and human was from RT-PCR of the L-type Ca2+ channel α1F-subunit with and of the to with and The which a was with and S. PubMed Scopus Google Scholar). RT-PCR and with and in a for of for for and for by a on a and by with The into and the the DNA of of Intracellular Ca2+ Ca2+ levels the Ca2+ ester to In Jurkat T cells human with μm for h in of cell was to of T cells for the with μm (+/-) Bay K 8644 μm a Jurkat T cells and human with also with μm nifedipine with extracellular Ca2+ in the for the Jurkat T cells with whereas human a of and which as a to activate Ca2+ the activate Ca2+ influx in The in intracellular Ca2+ concentration was through the of of nm and the of to In the of was to of the treatment (+/-) Bay K 8644 and nifedipine in the as a of in of T cells human in and with for to by with (+/-) Bay K 8644 μm Jurkat T cells also with μm μm nifedipine for by with μm (+/-) Bay K 8644 as a for kinase activation, Jurkat T cells with for Following cells in of in the of and Cell by in on and to was with kinase the in and for and with extracellular regulated kinase1/2 as a Jurkat T cells and in with of for and by a h cells with nifedipine for h by with for h activity was on the in the activity was in a IL-2 and IL-2 T cells human with nifedipine for h to a with nm 12-O-tetradecanoylphorbol 13-acetate was and cells for IL-2 concentration by a To the Ca2+ the of nifedipine, Jurkat T cells human with μm nifedipine for for h with nm μm The concentration of IL-2 in the was by IL-2 receptor expression was through by cells with human and Cell was assessed by cells with propidium iodide from mice cells with nifedipine for h with cells from mice for to with nifedipine in the in with nm and of and was by a as J. Immunol. 2001; PubMed Scopus Google Scholar). In from mice a receptor for the male antigen with μm 5-(and-6)-carboxyfluorescein diacetate, succinimidyl ester for into the of male by of nifedipine into the h Nifedipine was as a in and h the and cell cell in and with and by which is for with and on a of receptor CD8+ T cells in was by the of and cells in cell a of a of cellular cell was by the was to indicate the Ca2+ in T to Ca2+ influx through Ca2+ channels. studies that nifedipine with T lymphocyte proliferation we to the expression of an L-type Ca2+ channel in T lymphocytes. a RT-PCR a to the pore-forming α1F-subunit of an L-type was from T lymphocytes and used as for the the α1F-subunit was from human and is in Nat. 1998; 19: PubMed Scopus Google Scholar, M.J. Nat. 1998; 19: PubMed Scopus Google Scholar). In the studies α1F-subunit the α1F-subunit was in Nat. 1998; 19: PubMed Scopus Google Scholar). The expression by the of a we to that the from Jurkat T human and CD8+ T lymphocytes identity to the L-type Ca2+ channel α1F-subunit in human and The α1F-subunit is in human cells we to α1F-subunit expression in human of Ca2+ in Jurkat T Cell and by Ca2+ (+/-) Bay K 8644 that L-type Ca2+ channels to Ca2+ we the of the (+/-) Bay K 8644, on Ca2+ influx in human T lymphocytes. that the treatment of Jurkat T cells with Bay K 8644 in the of μm a in intracellular the of a Ca2+ influx pathway in these cells J. P. Mol. Google Scholar). However, the which of Bay K 8644 was and of Bay K 8644 L-type the was in with (+/-) Bay K 8644, a that the of Ca2+ influx through L-type Ca2+ channels 1999; PubMed Scopus Google Scholar). we to the effects of (+/-) Bay K 8644 treatment on Ca2+ influx in Jurkat T cells to the Jurkat T cells and human with (+/-) Bay K 8644, a in the of to Ca2+ was an in intracellular Ca2+ In Jurkat T cells and μm (+/-) Bay K 8644 induced a sustained in intracellular However, treatment of Jurkat T cells and with of (+/-) Bay K 8644 induced in Ca2+ In Jurkat T and μm (+/-) Bay K 8644 induced a sustained in Ca2+ treatment of human with μm (+/-) Bay K 8644 a transient Ca2+ influx that to the In the of extracellular Ca2+ in the μm (+/-) Bay K 8644 a in intracellular Ca2+ in Jurkat T cells human that (+/-) Bay K 8644 treatment with extracellular Ca2+ Ca2+ into these the significant Ca2+ entry into T lymphocytes. We also the effects of the Ca2+ to of the into T lymphocytes. The μm induced a and sustained Ca2+ influx in Jurkat T cells and human and L-type Ca2+ Nifedipine Ca2+ in Jurkat T Cell and is a of L-type Ca2+ channels and was used to further investigate the role of a Ca2+ channel in T lymphocytes. of the on nifedipine the of T lymphocytes the and we on the activation of T lymphocytes through the complex the of Jurkat T cells and human with nifedipine in the of extracellular Ca2+ in a in the of to Ca2+ A and A in the that nifedipine Ca2+ influx in Jurkat T cells and whereas the no Although nifedipine Ca2+ influx in the cells we to was a of Ca2+ L-type Ca2+ channels are the channels that Ca2+ influx channels to the Ca2+ during T lymphocyte activation. To we Ca2+ influx with extracellular Ca2+ to Ca2+ influx induced in the of extracellular In Jurkat T cells and a transient in intracellular from intracellular Ca2+ was extracellular Ca2+ was from the and transient Ca2+ was in Jurkat T cells with nifedipine in the of extracellular that nifedipine blocked Ca2+ influx in these However, in human of nifedipine Ca2+ influx the Ca2+ with no extracellular Ca2+ was to with μm nifedipine extracellular Ca2+ was We also nifedipine blocked Ca2+ from intracellular Ca2+ To investigate Jurkat T cells and human with nifedipine and in the of extracellular Ca2+ and Nifedipine treatment significantly the transient in Ca2+ from intracellular Ca2+ stores in Jurkat T whereas in human μm nifedipine the of Ca2+ from intracellular stores in these that (+/-) Bay K 8644 and nifedipine are used μm on and nonexcitable cell The concentration of used in these the concentration of Ca2+ channel in studies 1999; PubMed Scopus Google Scholar, PubMed Scopus Google Scholar). (+/-) Bay K 8644 and Nifedipine in Jurkat T and The in was to the Ca2+ influx through L-type Ca2+ channels activate signaling pathways in T lymphocyte activation. We the expression of the also as Erk1/2 a in intracellular Ca2+ through Ca2+ as and the activation of Erk1/2 in T lymphocytes Mol. Immunol. 1999; PubMed Scopus Google Scholar). The of the Ca2+ to of Jurkat T and human with activation of Erk1/2 that of Erk1/2 activation in T lymphocytes is through an in intracellular Ca2+ Mol. Immunol. 1999; PubMed Scopus Google Scholar). are to the kinase pathway in in T lymphocytes 2001; PubMed Scopus Google Scholar). In Jurkat T and μm (+/-) Bay K 8644 in a and transient of and which is to the of Erk1/2 activated with μm The activation of Erk1/2 with (+/-) Bay K 8644 was blocked by with In human (+/-) Bay K 8644 activate and activated with the The activation of with (+/-) Bay K 8644 was blocked by with The treatment of Jurkat T cells and human with activate that we also the effects of μm (+/-) Bay K 8644 on human that from and with and human the of activation (+/-) Bay K 8644 treatment as human for in with and is on of the T lymphocyte activation are by Ca2+ influx with nifedipine we Erk1/2 activation induced by (+/-) Bay K 8644 blocked by of Jurkat T cells with μm μm nifedipine, the significantly Erk1/2 activation induced by μm (+/-) Bay K 8644 a for Erk1/2 we Jurkat T cells with of Jurkat T cells through the complex induced activation of that the Ca2+ influx induced by (+/-) Bay K 8644 Erk1/2 activation. Nifedipine in Jurkat T Cell activation of the transcription factor is increased intracellular Ca2+ P. Mol. Cell. Biol. PubMed Scopus Google Scholar). We the in Ca2+ influx through L-type Ca2+ channels by nifedipine the activity of by an into Jurkat T of Jurkat T cells transcription to to the within the and the The of Jurkat T cells to to h Ca2+ channel activity by of Jurkat T cells with nifedipine in of activation in a of nifedipine that blocked Ca2+ influx, as μm nifedipine, significantly the activity of of nifedipine, as The activation in Jurkat T Jurkat T cells with a that the activate IL-2 and is by Nifedipine in Jurkat T Cell and IL-2 is a of T cell activation, we assessed Ca2+ channels with nifedipine IL-2 in Jurkat T cells and human In with the the of nifedipine on Ca2+ influx and activation nifedipine significantly IL-2 in cell and IL-2 μm The significantly IL-2 from Jurkat T cells human To the in IL-2 by nifedipine was to cell death induced by Jurkat T cells and human with for The cell was by In Jurkat T cells and human μm nifedipine a significant on cell with the of cells with and with and We the of nifedipine by the of intracellular Ca2+ in T treatment with was used to Ca2+ to the Jurkat T cells and human with nifedipine and indicated and IL-2 was as an of T cell activation. In cell of IL-2 by μm and μm nifedipine by the of However, the treatment of T cells with μm nifedipine by treatment. In the of nifedipine with was in human with Jurkat T expression was also on T cells and it was found that μm nifedipine significantly receptor expression. In Jurkat T cells μm nifedipine a in the of whereas in human with μm nifedipine a was with expression of T cells with and with Nifedipine investigate nifedipine the proliferation of T lymphocytes, we the effects of nifedipine on the induced by a mixed lymphocyte reaction Nifedipine significantly suppressed the proliferation of in a of nifedipine, including and splenocyte proliferation, whereas and μm nifedipine proliferation. was no significant of splenocyte proliferation by treatment with nifedipine induced splenocyte proliferation in we nifedipine the proliferation of an antigen T cell in vivo. To we the of CD8+ T cells into male mice with of nifedipine In male CD8+ T cells in the in to the male male mice with of nifedipine CD8+ T cell proliferation Nifedipine treatment in an increased of CD8+ T cells cell and significantly cells to with the We the of nifedipine in by of nifedipine h of nifedipine in to of the lead to a in the T cell proliferation with J.E. M.J. PubMed Scopus Google Scholar). In CD8+ T cells to the as the that nifedipine is L-type Ca2+ channels and a in the which lead to T cell proliferation We also the of CD8+ T cells in mice as a for no proliferation. the CD8+ T cells to the in the mice to the of the male antigen The in the of the was to that a L-type Ca2+ channel protein is in T lymphocytes. the of with the expression of a we by through RT-PCR that the L-type α1F-subunit is in human T lymphocytes. the of the that the is in T lymphocytes, which is a novel and in the In to the role of L-type Ca2+ channels in T lymphocytes, we that studies used to the of these channels in the plasma of numerous cell 1999; PubMed Scopus Google Scholar, PubMed Scopus Google Scholar, Annu. Rev. PubMed Google Scholar). In the we used the (+/-) Bay K 8644 and nifedipine, to further investigate the of L-type Ca2+ channels in T lymphocytes and to the contribution of Ca2+ influx by L-type Ca2+ channels during the T lymphocyte activation an intracellular Ca2+ we that (+/-) Bay K 8644 an on the Ca2+ channels of Jurkat T cells and human However, treatment with (+/-) Bay K 8644 Ca2+ influx in cell of and Jurkat T cells in a in intracellular We also that nifedipine Ca2+ influx, and significantly Ca2+ release from intracellular Ca2+ stores in Jurkat T cells through the we that nifedipine is L-type Ca2+ channels found in the plasma with effects on Ca2+ release from intracellular Although the of of confirmed by the on the of L-type VDCCs J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar, J. M.J. S. J. J. Biol. Full Text Full Text PDF PubMed Scopus Google are studies the effects of of on voltage-dependent potassium channels and potassium channels D.M. J. PubMed Google Scholar, J. PubMed Scopus Google Scholar, J. Google Scholar). these of in the J. PubMed Scopus Google that of nifedipine and the of Bay K 8644 an on current through and channels. is in to we that (+/-) Bay K 8644 an nifedipine Ca2+ influx in T lymphocytes. In (+/-) Bay K 8644 activate channel J. PubMed Scopus Google Scholar). we that the of the in was to of Ca2+ influx through L-type Ca2+ channels. effects of on current the are the of nifedipine used in of Ca2+ influx is still D.M. J. PubMed Google Scholar). that (+/-) Bay K 8644 and nifedipine Ca2+ influx in T lymphocytes, we Ca2+ influx through an L-type Ca2+ channel signaling as kinase that Ca2+ with the kinase signaling pathway in T lymphocytes by and which are of Erk1/2 and for Erk1/2 activation Mol. Immunol. 2000; PubMed Scopus Google Scholar). We that (+/-) Bay K 8644 and activation of and in Jurkat T activation of in human and that the activation of Erk1/2 by (+/-) Bay K 8644 blocked by with the that Ca2+ influx through an L-type Ca2+ channel the kinase signaling pathway during T lymphocyte activation. The activation in Jurkat T cells and T lymphocytes the human a sustained of intracellular Ca2+ to activity with T lymphocytes. We that the Ca2+ a in intracellular Ca2+ in human with Jurkat T which with a of Erk1/2 by in human In Ca2+ entry induced by (+/-) Bay K 8644 in human was transient with the sustained Ca2+ influx in Jurkat T the in the of Ca2+ influx in (+/-) Bay K 8644 Erk1/2 in Jurkat T and activation of activity in human To an L-type Ca2+ channel signaling events during T lymphocyte activation, we the effects of nifedipine on the activity of IL-2 and expression. We that Ca2+ influx with nifedipine the activity of in a in Jurkat T regulates the transcription of cytokine including we the effects of nifedipine on IL-2 and expression P. Mol. Cell. Biol. PubMed Scopus Google Scholar). In Jurkat T cells and human IL-2 was blocked in the of We confirmed that the in IL-2 by nifedipine was to a in Ca2+ influx and cell death the of cells significantly with nifedipine are with a that of human T lymphocyte proliferation by μm nifedipine was to J. Immunol. Google Scholar). We also that the in IL-2 by nifedipine by the of that of nifedipine are L-type Ca2+ channels and the of channels in T lymphocytes. expression was with of is with the current that the signaling for expression of the are for IL-2 PubMed Scopus Google Scholar). Ca2+ entry through L-type Ca2+ channels regulates activity and IL-2 a on expression. In to that an L-type Ca2+ channel Ca2+ influx during T lymphocyte activation, we also an L-type Ca2+ channel the proliferation of T lymphocytes. To we the proliferation of mouse through an in vitro and found that nifedipine mouse splenocyte proliferation in a Although the in vitro effects of nifedipine are no studies of T cell proliferation in vivo. We are the to that of nifedipine treatment the proliferation of CD8+ T lymphocytes in that Ca2+ influx through L-type Ca2+ channels is for sustained Ca2+ influx during T lymphocyte proliferation in vitro and in vivo. Taken the in that (+/-) Bay K 8644 and nifedipine T lymphocyte activation and proliferation. Although we for the of a L-type Ca2+ channel in the plasma membrane of T lymphocytes, Ca2+ channels also to the Ca2+ influx is in with the of ion channels in regulating Ca2+ influx in T lymphocytes. J. J. Biol. Full Text Full Text PDF PubMed Scopus Google that the receptor of ion is in in Jurkat T which is regulated through intracellular Ca2+ Although plays a significant role in mediating Ca2+ of a of Ca2+ influx in Jurkat T to the that as L-type Ca2+ channels are also in Ca2+ entry J. J. Biol. Full Text Full Text PDF PubMed Scopus Google Scholar). channels that are by intracellular Ca2+ also found in human T lymphocytes. S. 2001; PubMed Scopus Google that the protein is in human peripheral blood and Jurkat T cells and Ca2+ influx in to elevated levels of and and protein is also in Jurkat T cells and and Ca2+ influx through channel is activated by diacylglycerol P. J. PubMed Scopus Google Scholar). In with the from and the of protein expression in T lymphocytes, it is Ca2+ into T lymphocytes is through Ca2+ including and L-type Ca2+ channels. that the and of Ca2+ in T lymphocytes are a of channels necessary to the Ca2+ for T lymphocyte activation, proliferation and also the of of as nifedipine, for treatment of effects on T lymphocytes J. S. J. J. 1998; PubMed Scopus Google Scholar). nifedipine is by in the treatment of including and Annu. Rev. PubMed Google Scholar, 18: PubMed Scopus Google Scholar). In with nifedipine the of L-type VDCCs, which are for the of and Annu. Rev. PubMed Google Scholar). a that lymphocytes in with of nifedipine and IL-2 J. PubMed Scopus Google Scholar). We that of nifedipine T lymphocyte proliferation in the of nifedipine in the are the concentration of P. J. PubMed Scopus Google treatment with nifedipine as an the of with findings further into Ca2+ channel are In we and for the of an L-type Ca2+ channel in T lymphocytes. of the role of the L-type Ca2+ channel α1F-subunit the for a of the mechanisms Ca2+ influx in T lymphocytes and lead to the of novel to T lymphocyte activation and The from the the that an L-type Ca2+ channel is in the plasma membrane of T lymphocytes and that channel contributes to Ca2+ influx during T lymphocyte activation and proliferation. We and for the for the intracellular Ca2+ We and for and for with the We and for on the

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