TRPM2 channel

Channel name TRPM21,2,3,4,5,6,7
Description Nucleotide-sensing TRP channel
Other names TRPC7, LTRPC2
Molecular information Human unigene: Hs0.369759, chr. 21q22.3
Mouse unigene: Mm0.276762, chr. 10 C1
Associated subunits Not established
Functional assays Patch-clamp, calcium imaging
Current Weakly voltage-sensitive cation current
Conductance 60pS, 58pS (negative potentials); 76pS at positive potentials
H2O2-induced channel (52.3pS), β-NAD+-activated channel (59pS)
Ion selectivity Nonselective, permeant to Na+, Ca2+, and K+
Activation Redox sensor, activation by H2O2 and TNF-α; modulated by arachidonic acid
Inactivation Flufenamic acid, clotrimazole, econazole, PARP inhibitors
Activators ADP-ribose, β-NAD+, increased [Ca2+]i potentiates (EC50 = 340 nM)
Gating inhibitors None
Blockers None
Radioligands None
Channel distribution Brain, placenta, lung, spinal cord, spleen, lymphocytes
Physiological functions Not established
Mutations and pathophysiology Not established
Pharmacological significance Not established
  • chr., chromosome; NAD, nicotinamide adenine dinucleotide; TNF, tumor necrosis factor; PARP, poly(ADP-ribose) polymerase.

  • 1. Nagamine K, Kudoh J, Minoshima S, Kawasaki K, Asakawa S, Ito F, and Shimizu N (1998) Molecular cloning of a novel putative Ca2+ channel protein (TRPC7) highly expressed in brain. Genomics 54:124-131

  • 2. Perraud AL, Fleig A, Dunn CA, Bagley LA, Launay P, Schmitz C, Stokes AJ, Zhu Q, Bessman MJ, Penner R, et al. (2001) ADP-ribose gating of the calcium-permeable LTRPC2 channel revealed by Nudix motif homology. Nature (Lond) 411:595-599

  • 3. Sano Y, Inamura K, Miyake A, Mochizuki S, Yokoi H, Matsushime H, and Furuichi K (2001) Immunocyte Ca2+ influx system mediated by LTRPC2. Science (Wash DC) 293:1327-1330

  • 4. Hara Y, Wakamori M, Ishii M, Maeno E, Nishida M, Yoshida T, Yamada H, Shimizu S, Mori E, Kudoh J, et al. (2002) LTRPC2 Ca2+-permeable channel activated by changes in redox status confers susceptibility to cell death. Mol Cell 9:163-173

  • 5. Hill K, McNulty S, and Randall AD (2004) Inhibition of TRPM2 channels by the antifungal agents clotrimazole and econazole. Naunyn Schmiedeberg's Arch Pharmacol 370:227-237

  • 6. Fonfria E, Marshall IC, Benham CD, Boyfield I, Brown JD, Hill K, Hughes JP, Skaper SD, and McNulty S (2004) TRPM2 channel opening in response to oxidative stress is dependent on activation of poly(ADP-ribose) polymerase. Br J Pharmacol 143:186-192

  • 7. Kraft R, Grimm C, Grosse K, Hoffmann A, Sauerbruch S, Kettenmann H, Schultz G, Harteneck C (2004) Hydrogen peroxide, and ADP-ribose induce TRPM2-mediated calcium influx and cation currents in microglia. Am J Physiol Cell Physiol 286:C129-C137