The mechano-activated K+ channels TRAAK and TREK-1 control both warm and cold perception.
The sensation of cold or heat depends on the activation of specific nerve endings in the skin. This involves heat- and cold-sensitive excitatory transient receptor potential (TRP) channels. However, we show here that the mechano-gated and highly temperature-sensitive potassium channels of the TREK/TRAAK family, which normally work as silencers of the excitatory channels, are also implicated. They are important for the definition of temperature thresholds and temperature ranges in which excitation of nociceptor takes place and for the intensity of excitation when it occurs. They are expressed with thermo-TRP channels in sensory neurons. TRAAK and TREK-1 channels control pain produced by mechanical stimulation and both heat and cold pain perception in mice. Expression of TRAAK alone or in association with TREK-1 controls heat responses of both capsaicin-sensitive and capsaicin-insensitive sensory neurons. Together TREK-1 and TRAAK channels are important regulators of nociceptor activation by cold, particularly in the nociceptor population that is not activated by menthol.
Noël
Jacques
J
Université de Nice-Sophia Antipolis, CNRS UMR6097, Institut de Pharmacologie Moléculaire et Cellulaire, Institut Paul Hamel, Sophia Antipolis, Valbonne, France. jnoel@unice.fr
Zimmermann
Katharina
K
Busserolles
Jérome
J
Deval
Emanuel
E
Alloui
Abdelkrim
A
Diochot
Sylvie
S
Guy
Nicolas
N
Borsotto
Marc
M
Reeh
Peter
P
Eschalier
Alain
A
Lazdunski
Michel
M
D000818:Animals; D002478:Cells, Cultured; D003080:Cold Temperature; D004594:Electrophysiology; D005727:Ganglia, Spinal / Q000166:cytology; D006358:Hot Temperature; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D010146:Pain; D015221:Potassium Channels / Q000235:genetics / Q000502:physiology*; D024683:Potassium Channels, Tandem Pore Domain / Q000235:genetics / Q000502:physiology*; D011984:Sensory Receptor Cells / Q000166:cytology / Q000378:metabolism; D013697:Thermosensing / Q000235:genetics / Q000502:physiology*
C503433:Kcnk4 protein, mouse; D015221:Potassium Channels; D024683:Potassium Channels, Tandem Pore Domain; C103742:potassium channel protein TREK-1