Transient receptor potential 1 regulates capacitative Ca²⁺ entry and Ca²⁺ release from endoplasmic reticulum in B lymphocytes

Capacitative Ca²⁺ entry (CCE) activated by release/depletion of Ca²⁺ from internal stores represents a major Ca²⁺ influx mechanism in lymphocytes and other nonexcitable cells. Despite the importance of CCE in antigen-mediated lymphocyte activation, molecular components constituting this mechanism remain elusive. Here we demonstrate that genetic disruption of transient receptor potential (TRP)1 significantly attenuates both Ca²⁺ release-activated Ca²⁺ currents and inositol 1,4,5-trisphosphate (IP₃)-mediated Ca²⁺ release from endoplasmic reticulum (ER) in DT40 B cells. As a consequence, B cell antigen receptor-mediated Ca²⁺ oscillations and NF-AT activation are reduced in TRP1-deficient cells. Thus, our results suggest that CCE channels, whose formation involves TRP1 as an important component, modulate IP₃ receptor function, thereby enhancing functional coupling between the ER and plasma membrane in transduction of intracellular Ca²⁺ signaling in B lymphocytes.