TrpC1 is a membrane-spanning subunit of store-operated Ca(2+) channels in native vascular smooth muscle cells.
Mammalian counterparts of the Drosophila trp gene have been suggested to encode store-operated Ca(2+) channels. These specialized channels are widely distributed and may have a general function to reload Ca(2+) into sarcoplasmic reticulum as well as specific functions, including the control of cell proliferation and muscle contraction. Heterologous expression of mammalian trp genes enhances or generates Ca(2+) channel activity, but the crucial question of whether any of the genes encode native subunits of store-operated channels remains unanswered. We have investigated if TrpC1 protein (encoded by trp1 gene) is a store-operated channel in freshly isolated smooth muscle cells of resistance arterioles, arteries, and veins from human, mouse, or rabbit. Messenger RNA encoding TrpC1 was broadly expressed. TrpC1-specific antibody 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 Ca(2+) channel activity. The antibody is a powerful new tool for the study of mammalian trp1 gene product. The study shows that TrpC1 is a novel physiological Ca(2+) channel subunit in arterial smooth muscle cells.
Xu
S Z
SZ
School of Biomedical Sciences, University of Leeds, Leeds, UK.
Beech
D J
DJ
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001808:Blood Vessels / Q000378:metabolism; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D050052:TRPC Cation Channels; D019284:Thapsigargin / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D015220:Calcium Channels; D008565:Membrane Proteins; D012333:RNA, Messenger; D050052:TRPC Cation Channels; C096351:transient receptor potential cation channel, subfamily C, member 1; D019284:Thapsigargin; D002118:Calcium