title: TRPM4 is a Ca2+-activated nonselective cation channel mediating cell membrane depolarization.
abstract: Calcium-activated nonselective (CAN) cation channels are expressed in various excitable and nonexcitable cells supporting important cellular responses such as neuronal bursting activity, fluid secretion, and cardiac rhythmicity. We have cloned and characterized a second form of TRPM4, TRPM4b, a member of the TRP channel family, as a molecular candidate of a CAN channel. TRPM4b encodes a cation channel of 25 pS unitary conductance that is directly activated by [Ca2+]i with an apparent K(D) of approximately 400 nM. It conducts monovalent cations such as Na+ and K+ without significant permeation of Ca2+. TRPM4b is activated following receptor-mediated Ca2+ mobilization, representing a regulatory mechanism that controls the magnitude of Ca2+ influx by modulating the membrane potential and, with it, the driving force for Ca2+ entry through other Ca2+-permeable pathways.
authors.affiliation: Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
authors.forename: Pierre
authors.initials: P
authors.lastname: Launay
authors.forename: Andrea
authors.initials: A
authors.lastname: Fleig
authors.forename: Anne Laure
authors.initials: AL
authors.lastname: Perraud
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Scharenberg
authors.forename: Reinhold
authors.initials: R
authors.lastname: Penner
authors.forename: Jean Pierre
authors.initials: JP
authors.lastname: Kinet
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000737:chemistry* / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology*; D027682:Cation Transport Proteins; D002412:Cations / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism / Q000502:physiology*; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000502:physiology; D006801:Humans; D017136:Ion Transport; D007668:Kidney / Q000166:cytology; D008564:Membrane Potentials / Q000502:physiology; D008969:Molecular Sequence Data; D008970:Molecular Weight; D011188:Potassium / Q000378:metabolism; D017422:Sequence Analysis, DNA; D012964:Sodium / Q000378:metabolism; D050052:TRPC Cation Channels; D050053:TRPM Cation Channels
chemical_list: D015220:Calcium Channels; D027682:Cation Transport Proteins; D002412:Cations; D050052:TRPC Cation Channels; D050053:TRPM Cation Channels; C437888:TRPM4 protein, human; D012964:Sodium; D011188:Potassium; D002118:Calcium