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 Ca2+ 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 GTP gamma S, 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.