What's Bred in the Bone: Calcium Channels in Lymphocytes

Calcium (Ca²⁺) is an important second messenger in lymphocytes and is essential in regulating various intracellular pathways that control critical cell functions. Ca²⁺ channels are located in the plasma membrane and intracellular membranes, facilitating Ca²⁺ entry into the cytoplasm. Upon Ag receptor stimulation, Ca²⁺ can enter the lymphocyte via the Ca²⁺ release-activated Ca²⁺ channel found in the plasma membrane. The increase of cytosolic Ca²⁺ modulates signaling pathways, resulting in the transcription of target genes implicated in differentiation, activation, proliferation, survival, and apoptosis of lymphocytes. Along with Ca²⁺ release-activated Ca²⁺ channels, several other channels have been found in the membranes of T and B lymphocytes contributing to key cellular events. Among them are the transient receptor potential channels, the P2X receptors, voltage-dependent Ca²⁺ channels, and the inositol 1,4,5-trisphosphate receptor as well as the N-methyl-d-aspartate receptors. In this article, we review the contributions of these channels to mediating Ca²⁺ currents that drive specific lymphocyte functions.