T Cell Receptor Mediated Calcium Entry Requires Alternatively Spliced Ca(V)1.1 Channels

The process of calcium entry in T cells is a multichannel and multi-step process. We have studied the requirement for L-type calcium channels (Ca(v)1.1) alpha 1S subunits during calcium entry after TCR stimulation. High expression levels of Ca(v)1.1 channels were detected in activated T cells. Sequencing and cloning of Ca(v)1.1 channel cDNA from T cells revealed that a single splice variant is expressed. This variant lacks exon 29, which encodes the linker region adjacent to the voltage sensor, but contains five new N-terminal exons that substitute for exons 1 and 2, which are found in the Ca(v)1.1 muscle counterpart. Overexpression studies using cloned T cell Ca(v)1.1 in 293HEK cells (that lack TCR) suggest that the gating of these channels was altered. Knockdown of Ca(v)1.1 channels in T cells abrogated calcium entry after TCR stimulation, suggesting that Ca(v)1.1 channels are controlled by TCR signaling.