Molecular and functional characterization of a novel mouse transient receptor potential protein homologue TRP7 - Ca2+-permeable cation channel that is constitutively activated and enhanced by stimulation of G protein-coupledreceptor

Characterization of mammalian homologues of Drosophila transient receptor p otential protein (TRP) is an important clue to understand molecular mechani sms underlying Ca2+ influx activated in response to stimulation of G(q) pro tein-coupled receptors in vertebrate cells. Here we have isolated cDNA enco ding a novel seventh mammalian TRP homologue, TRP7, from mouse brain. TRP7 showed abundant RNA expression in the heart, lung, and eye and moderate exp ression in the brain, spleen, and testis. TRP7 recombinantly expressed in h uman embryonic kidney cells exhibited distinctive functional features, comp ared with other TRP homologues. Basal influx activity accompanied by reduct ion in Ca2+ release from internal stores was characteristic of TRP7-express ing cells but was by far less significant in cells expressing TRP3, which i s structurally the closest to TRP7 in the TRP family. TRP7 induced Ca2+ inf lux in response to ATP receptor stimulation at ATP concentrations lower tha n those necessary for activation of TRP3 and for Ca2+ release from the intr acellular store, which suggests that the TRP7 channel is activated independ ently of Ca2+ release. In fact, TRP7 expression did not affect capacitative Ca2+ entry induced by thapsigargin, whereas TRP7 greatly potentiated Mn2influx induced by diacylglycerols without involvement of protein kinase C. Nystatin-perforated and conventional whole-cell patch clamp recordings from TRP7-expressing cells demonstrated the constitutively activated and ATP-en hanced inward cation currents, both of which were initially blocked and the n subsequently facilitated by extracellular Ca2+ at a physiological concent ration. Impairment of TRP7 currents by internal perfusion of the Ca2+ chela tor 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid revealed an es sential role of intracellular Ca2+ in activation of TRP7, and their potent activation by the diacylglycerol analogue suggests that the TRP7 channel is a new member of diacylglycerol-activated cation channels. Relative permeab ilities indicate that TRP7 is slightly selective to divalent cations. Thus, our findings reveal an interesting correspondence of TRP7 to the backgroun d and receptor stimulation-induced cation currents in various native system s.