title: A dynamic set point for thermal adaptation requires phospholipase C-mediated regulation of TRPM8 in vivo.
abstract: The ability to sense and respond to thermal stimuli at varied environmental temperatures is essential for survival in seasonal areas. In this study, we show that mice respond similarly to ramping changes in temperature from a wide range of baseline temperatures. Further investigation suggests that this ability to adapt to different ambient environments is based on rapid adjustments made to a dynamic temperature set point. The adjustment of this set point requires transient receptor potential cation channel, subfamily member 8 (TRPM8), but not transient receptor potential cation channel, subfamily A, member 1 (TRPA1), and is regulated by phospholipase C (PLC) activity. Overall, our findings suggest that temperature response thresholds in mice are dynamic, and that this ability to adapt to environmental temperature seems to mirror the in vitro findings that PLC-mediated hydrolysis of phosphoinositol 4,5-bisphosphate modulates TRPM8 activity and thereby regulates the response thresholds to cold stimuli.
authors.affiliation: Washington University Pain Center and Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110, USA; Neuroscience Program, Washington University School of Medicine, St. Louis, MO 63110, USA; Medical Scientist Training Program, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Brenner
authors.affiliation: Washington University Pain Center and Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Judith P
authors.initials: JP
authors.lastname: Golden
authors.affiliation: Washington University Pain Center and Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Sherri K
authors.initials: SK
authors.lastname: Vogt
authors.affiliation: Department of Biological Structure University of Washington, Seattle, WA 98195, USA; Neurobiology and Behavior Graduate Program, University of Washington, Seattle, WA 98195, USA.
authors.forename: Ajay
authors.initials: A
authors.lastname: Dhaka
authors.affiliation: Washington University Pain Center and Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Gina M
authors.initials: GM
authors.lastname: Story
authors.affiliation: Washington University Pain Center and Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110, USA; Neuroscience Program, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: gereaur@wustl.edu.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Gereau
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology*; D000818:Animals; D051379:Mice; D050053:TRPM Cation Channels / Q000235:genetics / Q000378:metabolism*; D013696:Temperature; D013697:Thermosensing / Q000502:physiology*; D010738:Type C Phospholipases / Q000378:metabolism*
chemical_list: D050053:TRPM Cation Channels; C492297:TRPM8 protein, mouse; D010738:Type C Phospholipases
keywords: Adaptation; Cold; Heat; PIP2; Pain; Phospholipase C; TRPA1; TRPM8; Thermosensation
references.citation: Nature. 2007 Jul 12;448(7150):204-8
references.pmid: 17538622
references.citation: J Biol Chem. 2013 May 3;288(18):12818-27
references.pmid: 23508958
references.citation: Nat Commun. 2013;4:2179
references.pmid: 23863968
references.citation: Brain Res. 1982 Jul 29;244(2):279-87
references.pmid: 7116176
references.citation: J Neurophysiol. 1970 Jul;33(4):518-26
references.pmid: 4988213
references.citation: J Neurosci. 2007 Oct 31;27(44):12067-77
references.pmid: 17978048
references.citation: Neurosci Bull. 2012 Apr;28(2):145-54
references.pmid: 22466125
references.citation: Eur J Neurosci. 2007 Nov;26(9):2516-23
references.pmid: 17970723
references.citation: Pflugers Arch. 2009 Oct;458(6):1093-102
references.pmid: 19669158
references.citation: Neuron. 2007 May 3;54(3):371-8
references.pmid: 17481391
references.citation: Br J Pharmacol. 2010 Jul;160(6):1293-4
references.pmid: 20590620
references.citation: J Neurosci. 2005 Feb 2;25(5):1304-10
references.pmid: 15689568
references.citation: Pain. 1992 Sep;50(3):355-363
references.pmid: 1333581
references.citation: J Gen Physiol. 2011 Feb;137(2):173-95
references.pmid: 21282398
references.citation: J Neurosci. 2013 Feb 13;33(7):2837-48
references.pmid: 23407943
references.citation: Cell. 2003 Mar 21;112(6):819-29
references.pmid: 12654248
references.citation: J Pain. 2010 Jun;11(6):588-99
references.pmid: 20015699
references.citation: PLoS One. 2012;7(6):e39765
references.pmid: 22745825
references.citation: J Neurosci. 2007 Dec 12;27(50):13680-90
references.pmid: 18077679
references.citation: J Neurosci. 2006 Nov 29;26(48):12512-25
references.pmid: 17135413
references.citation: J Physiol. 1995 Jun 15;485 ( Pt 3):767-74
references.pmid: 7562615
references.citation: Neurosci Lett. 2009 Jul 17;458(2):93-5
references.pmid: 19375484
references.citation: Mol Pain. 2007 Dec 17;3:40
references.pmid: 18086313
references.citation: Neuron. 2006 Apr 20;50(2):277-89
references.pmid: 16630838
references.citation: J Neurophysiol. 1997 Apr;77(4):2049-60
references.pmid: 9114254
references.citation: J Physiol. 1995 Jun 15;485 ( Pt 3):753-65
references.pmid: 7562614
references.citation: J Neurosci. 2007 Oct 17;27(42):11412-5
references.pmid: 17942735
references.citation: J Neurophysiol. 1970 Jul;33(4):508-17
references.pmid: 4988212
references.citation: Science. 2005 Mar 4;307(5714):1468-72
references.pmid: 15746429
references.citation: Pain. 2010 Aug;150(2):340-350
references.pmid: 20542379
references.citation: J Neurophysiol. 1993 May;69(5):1684-99
references.pmid: 8509832
references.citation: J Neurosci. 2013 Mar 27;33(13):5533-41
references.pmid: 23536068
references.citation: J Neurosci. 2013 Apr 3;33(14):6154-9
references.pmid: 23554496
references.citation: Nat Neurosci. 2011 May;14(5):595-602
references.pmid: 21460831
references.citation: Nature. 1999 Apr 1;398(6726):436-41
references.pmid: 10201375
references.citation: Proc Natl Acad Sci U S A. 2009 Jan 27;106(4):1273-8
references.pmid: 19144922
references.citation: Neuron. 2007 May 3;54(3):379-86
references.pmid: 17481392
references.citation: Mol Pain. 2012 Jul 28;8:55
references.pmid: 22839205
references.citation: J Biol Chem. 2009 Jan 16;284(3):1570-82
references.pmid: 19019830
references.citation: Neuron. 2010 Jun 10;66(5):671-80
references.pmid: 20547126
references.citation: J Neurosci. 2013 May 29;33(22):9283-94
references.pmid: 23719797
references.citation: Nature. 2004 Aug 12;430(7001):748-54
references.pmid: 15306801
references.citation: Nat Neurosci. 2005 May;8(5):626-34
references.pmid: 15852009
references.citation: Proc Natl Acad Sci U S A. 2007 Aug 14;104(33):13525-30
references.pmid: 17686976