TRPM8 mechanism of autonomic nerve response to cold in respiratory airway.
Breathing cold air without proper temperature exchange can induce strong respiratory autonomic responses including cough, airway constriction and mucosal secretion, and can exacerbate existing asthma conditions and even directly trigger an asthma attack. Vagal afferent fiber is thought to be involved in the cold-induced respiratory responses through autonomic nerve reflex. However, molecular mechanisms by which vagal afferent fibers are excited by cold remain unknown. Using retrograde labeling, immunostaining, calcium imaging, and electrophysiological recordings, here we show that a subpopulation of airway vagal afferent nerves express TRPM8 receptors and that activation of TRPM8 receptors by cold excites these airway autonomic nerves. Thus activation of TRPM8 receptors may provoke autonomic nerve reflex to increase airway resistance. This putative autonomic response may be associated with cold-induced exacerbation of asthma and other pulmonary disorders, making TRPM8 receptors a possible target for prevention of cold-associated respiratory disorders.
Xing
Hong
H
Department of Oral & Maxillofacial Surgery and Diagnostic Sciences, McKnight Brain Institute and College of Dentistry, University of Florida, Gainesville, Florida 32610, USA. hongxing@ufl.edu
Ling
Jennifer X
JX
Chen
Meng
M
Johnson
Richard D
RD
Tominaga
Makoto
M
Wang
Cong-Yi
CY
Gu
Jianguo
J
D000344:Afferent Pathways / Q000502:physiology; D000403:Airway Resistance / Q000502:physiology; D000818:Animals; D017776:Autonomic Pathways / Q000502:physiology*; D003080:Cold Temperature; D051381:Rats; D017207:Rats, Sprague-Dawley; D012137:Respiratory System / Q000294:innervation*; D050053:TRPM Cation Channels / Q000502:physiology*; D014630:Vagus Nerve / Q000502:physiology
D050053:TRPM Cation Channels; C498947:Trpm8 protein, rat