Requirement of Voltage-Gated Calcium Channel ß4 Subunit for T Lymphocyte Functions

Calcium is known to play vital roles in diverse physiological processes, and it is known that voltage-gated calcium channels (Ca v ) mediate calcium influx in excitable cells. However, no consensus exists on the molecular identity of the calcium channels present in nonexcitable cells such as T lymphocytes. Here, we demonstrate that T lymphocytes express both regulatory β 4 and poreforming Ca v 1 α 1 subunits of Ca v channels. Ca v β 4 -mutant T lymphocytes fail to acquire normal functions and display impairment in the calcium response, activation of the transcription factor NFAT, and cytokine production. Although Ca v 1 channels of lymphocytes retain their voltage dependency, T cell receptor stimulation dramatically increases channel opening, providing a new mechanism for calcium entry in lymphocytes.