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

In T lymphocytes, sustained calcium (Ca[sup 2+]) influx through Ca[sup 2+] channels localized in the plasma membrane is critical for T cell activation and proliferation. Previous studies indicated that voltage-dependent Ca[sup 2+] channels (VDCCs) play a role in Ca[sup 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 α[sub 1F]-subunit of an L-type Ca[sup 2+] channel in T lymphocytes. Its identity was confirmed by DNA sequencing. To further investigate the contribution of Ca[sup 2+] influx through VDCCs, we assessed the effects of the 1,4-dihydropyridine L-type Ca[sup 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[sup 2+] and induced the activation of phosphoextracellular-regulated kinase ½ (Erk½), whereas nifedipine blocked Ca[sup 2+] influx, the activity of Erk½ 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[sup +] T cells in transplanted male mice in vivo. Taken together these novel findings indicate that an L-type Ca[sup 2+] channel plays a significant role in the Ca[sup 2+] influx pathways mediating T lymphocyte activation and proliferation in vitro and in vivo. [ABSTRACT FROM AUTHOR]