The role of canonical transient receptor potential 7 in B-cell receptor-activated channels

Phospholipase C signaling stimulates Ca²⁺ entry across the plasma membrane through multiple mechanisms. Ca²⁺ store depletion stimulates store-operated Ca²⁺-selective channels, or alternatively, other phospholipase C-dependent events activate Ca²⁺-permeable non-selective cation channels. Transient receptor potential 7 (TRPC7) is a non-selective cation channel that can be activated by both mechanisms when ectopically expressed, but the regulation of native TRPC7 channels is not known. We knocked out TRPC7 in DT40 B-cells, which expresses both forms of Ca ²⁺ entry. No difference in the store-operated current I _crac was detected between TRPC7^-/- and wild-type cells. Wild-type cells demonstrated non-store-operated cation entry and currents in response to activation of the B-cell receptor or protease-activated receptor 2, intracellular dialysis with GTPγS, or application of the synthetic diacylglycerol oleyl-acetyl-glycerol. These responses were absent in TRPC7 ^-/- cells but could be restored by transfection with human TRPC7. In conclusion, in B-lymphocytes, TRPC7 appeared to participate in the formation of ion channels that could be activated by phospholipase C-linked receptors. This represents the first demonstration of a physiological function for endogenous TRPC7 channels.