title: Ambient temperature affects the temperature threshold for TRPM8 activation through interaction of phosphatidylinositol 4,5-bisphosphate.
abstract: Cold sensation is an important and fundamental sense for animals and it is known to be affected by ambient temperature. Transient Receptor Potential Melastatin 8 (TRPM8), a nonselective cation channel expressed in a subset of peripheral afferent fibers, acts as a cold sensor, having an activation threshold of ∼28°C. Although the cold temperature threshold of TRPM8 is affected by menthol or pH, ambient temperature has not been reported to affect it. Because the cold temperature threshold was thought to be unchanged by alterations in ambient temperature, the relativity of temperature sensing in different ambient temperatures could not be understood at the level of molecular function of thermosensitive TRP channels. Here, we show that ambient temperature changed the temperature threshold for activation of human and rat TRPM8 in a heterologous expression system and cold responses in mouse DRG neurons. Moreover, reducing the level of cellular phosphatidylinositol 4,5-bisphosphate (PIP2) attenuated changes in the cold temperature threshold after alterations in ambient temperature. A single amino acid mutation at position 1008 in the C terminus of TRPM8 (arginine to glutamine) also attenuated changes in the cold temperature threshold induced by ambient temperature. These findings suggest that ambient temperature does affect the temperature threshold for TRPM8 activation through interaction of PIP2.
authors.affiliation: Section of Cell Signaling, Okazaki Institute for Integrative Bioscience, National Institutes of Natural Sciences, Okazaki 444-8787, Japan. fujita-f@mandom.co.jp
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Fujita
authors.forename: Kunitoshi
authors.initials: K
authors.lastname: Uchida
authors.forename: Masayuki
authors.initials: M
authors.lastname: Takaishi
authors.forename: Takaaki
authors.initials: T
authors.lastname: Sokabe
authors.forename: Makoto
authors.initials: M
authors.lastname: Tominaga
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D015232:Dinoprostone / Q000494:pharmacology; D020536:Enzyme Activators / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000166:cytology; D057809:HEK293 Cells; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics; D051379:Mice; D009154:Mutation / Q000235:genetics; D018408:Patch-Clamp Techniques; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism*; D051381:Rats; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000502:physiology; D013449:Sulfonamides / Q000494:pharmacology; D050053:TRPM Cation Channels / Q000235:genetics / Q000378:metabolism*; D013696:Temperature; D013697:Thermosensing / Q000187:drug effects / Q000235:genetics*; D014162:Transfection; D000096926:Benzenesulfonamides
chemical_list: D002118:Calcium; D015232:Dinoprostone; D020536:Enzyme Activators; D019269:Phosphatidylinositol 4,5-Diphosphate; D013449:Sulfonamides; D050053:TRPM Cation Channels; C473783:2,4,6-trimethyl-N-(meta-3-trifluoromethylphenyl)benzenesulfonamide; D000096926:Benzenesulfonamides
references.citation: Proc Natl Acad Sci U S A. 2004 Oct 26;101(43):15494-9
references.pmid: 15492228
references.citation: J Physiol. 2001 Jan 1;530(Pt 1):1-19
references.pmid: 11136854
references.citation: J Physiol. 2007 May 15;581(Pt 1):155-74
references.pmid: 17317754
references.citation: Sci STKE. 2001 Dec 04;2001(111):re19
references.pmid: 11734659
references.citation: Nature. 1997 Oct 23;389(6653):816-24
references.pmid: 9349813
references.citation: Nature. 2001 Jun 21;411(6840):957-62
references.pmid: 11418861
references.citation: Naturwissenschaften. 1990 Jun;77(6):288-9
references.pmid: 2388701
references.citation: Pain. 2010 Aug;150(2):340-350
references.pmid: 20542379
references.citation: Nat Cell Biol. 2012 Aug;14(8):851-8
references.pmid: 22750945
references.citation: Mol Pain. 2005 Jan 17;1:3
references.pmid: 15813989
references.citation: Nat Neurosci. 2005 May;8(5):626-34
references.pmid: 15852009
references.citation: Proc Natl Acad Sci U S A. 2008 Jun 10;105(23):7970-5
references.pmid: 18524949
references.citation: J Physiol. 2011 Dec 15;589(Pt 24):6007-27
references.pmid: 22005680
references.citation: J Neurosci. 2011 Aug 10;31(32):11425-36
references.pmid: 21832173
references.citation: Cell. 2002 Mar 8;108(5):705-15
references.pmid: 11893340
references.citation: J Neurobiol. 2004 Oct;61(1):3-12
references.pmid: 15362149
references.citation: J Gen Physiol. 2005 Sep;126(3):243-62
references.pmid: 16129772
references.citation: Nat Neurosci. 2006 Apr;9(4):493-500
references.pmid: 16520735
references.citation: J Neurosci. 2004 Jun 9;24(23):5364-9
references.pmid: 15190109
references.citation: Nat Cell Biol. 2002 May;4(5):329-36
references.pmid: 11941371
references.citation: Neuron. 2004 Sep 16;43(6):859-69
references.pmid: 15363396
references.citation: J Neurosci. 2010 Sep 15;30(37):12526-34
references.pmid: 20844147
references.citation: J Biol Chem. 2009 Apr 3;284(14):9215-24
references.pmid: 19176480
references.citation: J Neurosci. 2005 Feb 16;25(7):1674-81
references.pmid: 15716403
references.citation: Nature. 2002 Mar 7;416(6876):52-8
references.pmid: 11882888
references.citation: J Neurochem. 2007 Jan;100(1):211-24
references.pmid: 17074062
references.citation: J Biol Chem. 2009 Jan 16;284(3):1570-82
references.pmid: 19019830
references.citation: Proc Natl Acad Sci U S A. 2003 Dec 9;100(25):15160-5
references.pmid: 14657398
references.citation: Pflugers Arch. 2007 Oct;455(1):157-68
references.pmid: 17479281
references.citation: Proc Natl Acad Sci U S A. 2012 Apr 24;109(17):6745-50
references.pmid: 22493272
references.citation: Proc Natl Acad Sci U S A. 1995 Jun 6;92(12):5317-21
references.pmid: 7777504
references.citation: Nature. 2004 Aug 12;430(7001):748-54
references.pmid: 15306801