title: Ionic channels formed by TRPC4.
abstract: TRPC4 (transient receptor potential canonical 4) is a member of the TRPC sub-family and, within this sub-family, TRPC4 is most closely related to TRPC5. A number of splice variants of TRPC4 have been identified, whereby TRPC4alpha and TRPC4beta appear to be the most abundant isoforms in various species. TRPC4alpha comprises six transmembrane segments and the N- and C-termini are located intracellularly. Additionally, TRPC4alpha shares other structural features with members of the TRPC sub-group, including ankyrin-like repeats, coiled-coil regions and binding sites for calmodulin and IP3 receptors. Three calmodulin-binding domains have been identified in the C-terminus of TRPC4alpha. TRPC4beta lack 84 amino acids in the C-terminus, which correspond to the last two calmodulin-binding sites of TRPCalpha. The first and last calmodulin-binding domains of TRPC4alpha overlap with binding sites for the N- and C-termini of IP3 receptors. The ionic channels formed by TRPC4 appear to be Ca(2+)-permeable, although there is a considerably discrepancy in the degree of Ca2+ selectivity. Studies with mice lacking TRPC4 (TRPC4(-/-)) suggest an important role for TRPC4 in supporting Ca2+ entry. The defect in Ca2+ entry in TRPC4(-/-) mice appears to be associated with a reduction of the vasorelaxation of arteries, vascular permeability in the lung and neurotransmitter release from thalamic dendrites.
authors.affiliation: Pharmakologie und Toxikologie, Universität des Saarlandes, 66421 Homburg, Germany. adolfo.cavalie@uniklinikum-saarland.de
authors.forename: A
authors.initials: A
authors.lastname: Cavalié
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001711:Biotransformation / Q000187:drug effects; D006801:Humans; D007473:Ion Channels / Q000502:physiology*; D011485:Protein Binding; D050052:TRPC Cation Channels / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*
chemical_list: D000596:Amino Acids; D007473:Ion Channels; D050052:TRPC Cation Channels; C489571:TRPC4 ion channel