TrpC1 is a membrane-spanning subunit of store-operated Ca2+ channels in native vascular smooth muscle cells

Mammalian counterparts of the Drosophila trp gene have been suggested to en code store-operated Ca2+ channels. These specialized channels are widely di stributed and may have a general function to reload Ca2+ into sarcoplasmic reticulum as well as specific functions, including the control of cell prol iferation and muscle contraction. Heterologous expression of mammalian trp genes enhances or generates Ca2+ channel activity, but the crucial question of whether any of the genes encode native subunits of store-operated chann els remains unanswered. We have investigated if TrpC1 protein (encoded by t rp1 gene) is a store-operated channel in freshly isolated smooth muscle cel ls of resistance arterioles, arteries, and veins from human, mouse, or rabb it. Messenger RNA encoding TrpC1 was broadly expressed, TrpC1-specific anti body targeted to peptide predicted to contribute to the outer vestibule of TrpC1 channels revealed that TrpC1 is localized to the plasma membrane and has an extracellular domain. Peptide-specific binding of the antibody had a functional effect, selectively blocking store-operated Ca2+ channel activi ty. The antibody is a powerful new tool for the study of mammalian trp1 gen e product. The study shows that TrpC1 is a novel physiological Ca2+ channel subunit in arterial smooth muscle cells.