Non-voltage-gated L-type Ca2+ channels in human T cells: pharmacology and molecular chracterization of the major alpha pore-forming and beta auxiliary subunits

In T lymphocytes, engagement of the antigen receptor leads to a biphasic Ca2+ flux consisting of a mobilization of Ca2+ from intracellular stores followed by a lower but sustained elevation that is dependent on extracellular Ca2+. The prolonged Ca2+ flux is required for activation of transcription factors and for subsequent activation of the T cell. Ca2+ influx requires as yet unidentified Ca2+ channels, which potentially play a role in T cell activation. Here we present evidence that human T cells express a non-voltage-gated Ca2+ channel related to L-type voltage-gated Ca2+ channels. Drugs that block classical L-type channels inhibited the initial phase of the antigen receptor-induced Ca2+ flux and could also inhibit the sustained phase of the Ca2(+) signal suggesting a role for the L-type Ca2+ channel in antigen receptor signaling. T cells expressed transcripts for the alpha(1)1.2 and alpha(1)1.3 pore-forming subunits of L-type voltage-gated Ca2+ channels and transcripts for all four known beta-subunits including several potential new splice variants. Jurkat T leukemia cells expressed a small amount of full-length alpha(1)1.2 protein but the dominant form was a truncated protein identical in size to a truncated alpha(1)1.2 protein known to be expressed in B lymphocytes. They further expressed a truncated form of the alpha(1)1.3 subunit and auxiliary beta1- and beta3-subunit proteins. Our data strongly suggest that functional but non-voltage-gated L-type Ca2+ channels are expressed at the plasma membrane in T cells and play a role in the antigen receptor-mediated Ca2+ flux in these cells.