TY - JOUR
T1 - TRPM5 is a voltage-modulated and Ca2+-activated monovalent selective cation channel
AU - Hofmann, Thomas
AU - Chubanov, Vladimir
AU - Gudermann, Thomas
AU - Montell, Craig
PY - 2003/7/1
Y1 - 2003/7/1
N2 - The TRPM subfamily of mammalian TRP channels displays unusually diverse activation mechanisms and selectivities [1]. One member of this subfamily, TRPM5, functions in taste receptor cells and has been reported to be activated through G protein-coupled receptors linked to phospholipase C [2, 3]. However, the specific mechanisms regulating TRPM5 have not been described. Here, we demonstrate that TRPM5 is a monovalent-specific cation channel with a 23 pS unitary conductance. TRPM5 does not display constitutive activity. Rather, it is activated by stimulation of a receptor pathway coupled to phospholipase C and by IP3-mediated Ca2+ release. Gating of TRPM5 was dependent on a rise in Ca2+ because it was fully activated by Ca2+. Unlike any previously described mammalian TRP channel, TRPM5 displayed voltage modulation and rapid activation and deactivation kinetics upon receptor stimulation. The most closely related protein, the Ca2+-activated monovalent-selective cation channel TRPM4b, also showed voltage modulation, although with slower relaxation kinetics than TRPM5. Taken together, the data demonstrate that TRPM5 and TRPM4b represent the first examples of voltage-modulated, Ca2+-activated, monovalent cation channels (VCAMs). The voltage modulation and rapid kinetics provide TRPM5 with an excellent set of properties for participating in signaling in taste receptors and other excitable cells.
AB - The TRPM subfamily of mammalian TRP channels displays unusually diverse activation mechanisms and selectivities [1]. One member of this subfamily, TRPM5, functions in taste receptor cells and has been reported to be activated through G protein-coupled receptors linked to phospholipase C [2, 3]. However, the specific mechanisms regulating TRPM5 have not been described. Here, we demonstrate that TRPM5 is a monovalent-specific cation channel with a 23 pS unitary conductance. TRPM5 does not display constitutive activity. Rather, it is activated by stimulation of a receptor pathway coupled to phospholipase C and by IP3-mediated Ca2+ release. Gating of TRPM5 was dependent on a rise in Ca2+ because it was fully activated by Ca2+. Unlike any previously described mammalian TRP channel, TRPM5 displayed voltage modulation and rapid activation and deactivation kinetics upon receptor stimulation. The most closely related protein, the Ca2+-activated monovalent-selective cation channel TRPM4b, also showed voltage modulation, although with slower relaxation kinetics than TRPM5. Taken together, the data demonstrate that TRPM5 and TRPM4b represent the first examples of voltage-modulated, Ca2+-activated, monovalent cation channels (VCAMs). The voltage modulation and rapid kinetics provide TRPM5 with an excellent set of properties for participating in signaling in taste receptors and other excitable cells.
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U2 - 10.1016/S0960-9822(03)00431-7
DO - 10.1016/S0960-9822(03)00431-7
M3 - Article
C2 - 12842017
AN - SCOPUS:0037672155
SN - 0960-9822
VL - 13
SP - 1153
EP - 1158
JO - Current Biology
JF - Current Biology
IS - 13
ER -