Direct activation of trpl cation channels by G alpha(11) subunits

G proteins of the G(q/11) subfamily functionally couple cell surface receptors to phospholipase C beta (PLC beta) isoforms, Stimulation of PLC beta induces Ca2+ elevation by inositol 1,4,5-trisphosphate (InsP(3))-mediated Ca2+ release and store-dependent 'capacitative' Ca2+ entry through Ca2+-permeable channels. The Drosophila trp gene, as well as some human trp homologs, code for such store-operated channels, The related trp-like (trpl) gene product also forms a Ca2+-permeable cation channel, but is not activated by store depletion, Co-expression of the constitutively active G(q) subfamily member G alpha(11) (G alpha*(11)) with trpl enhanced trpl currents 33-fold in comparison with co-expression of trpl with other G alpha isoforms or G beta gamma complexes. This activation could not be attributed to signals downstream of PLC beta. In particular, InsP(3) infusion, modulation of protein kinase C activity or elevation of intracellular calcium concentration failed to induce trpl currents. In contrast, purified G alpha*(11) (but not other G protein subunits) activated trpl channels in inside-out patches. We conclude that trpl is regulated by G(11) proteins in a membrane-confined manner not involving cytosolic factors. Thus, G proteins of the G(q) subfamily may induce Ca2+ entry not only indirectly via store-operated mechanisms but also by directly stimulating cation channels.