TRPM8 mRNA Is Expressed in a Subset of Cold-Responsive Trigeminal Neurons From Rat

• Published in: Journal of neurophysiology 2003-07, Vol.90 (1), p.515-520
• Main Authors: Nealen, Michele L, Gold, Michael S, Thut, Paul D, Caterina, Michael J
• Format: Article
• Language: English
• Subjects: Animals; Body Temperature Regulation; Calcium - physiology; Calcium Signaling; Cell Culture Techniques; Cold Temperature; DNA Primers; Fluorometry; Ion Channels - analysis; Ion Channels - genetics; Ion Channels - physiology; Male; Neoplasm Proteins - analysis; Neoplasm Proteins - genetics; Neoplasm Proteins - physiology; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - analysis; Thermoreceptors - physiology; Trigeminal Ganglion - chemistry; Trigeminal Ganglion - physiology; TRPM Cation Channels; TRPM8 protein
• ISSN: 0022-3077; 1522-1598
• DOI: 10.1152/jn.00843.2002

1 Departments of Biological Chemistry and Neuroscience, Johns Hopkins School of Medicine, Baltimore, Maryland 21205; and 2 Departments of Oral and Craniofacial Biological Sciences and 3 Anatomy and Neurobiology, University of Maryland Dental School, Baltimore, Maryland 21201 Submitted 23 September 2002; accepted in final form 5 March 2003 Recent electrophysiological studies of cultured dorsal root and trigeminal ganglion neurons have suggested that multiple ionic mechanisms underlie the peripheral detection of cold temperatures. Several candidate "cold receptors," all of them ion channel proteins, have been implicated in this process. One of the most promising candidates is TRPM8, a nonselective cationic channel expressed in a subpopulation of sensory neurons that is activated both by decreases in temperature and the cooling compound menthol. However, evidence for the expression of TRPM8 in functionally defined cold-sensitive neurons has been lacking. Here, we combine fluorometric calcium imaging of cultured rat trigeminal neurons with single-cell RT-PCR to demonstrate that there are distinct subpopulations of cold responsive neurons and that TRPM8 likely contributes to cold transduction in one of them. TRPM8 is preferentially expressed within a subset of rapidly responsive, low-threshold (approximately 30°C), cold-sensitive neurons. A distinct class of slowly responsive cold-sensitive neurons that is activated at lower temperatures (approximately 20°C) generally lacks detectable TRPM8 mRNA. Together with previous findings, our data support the notion that cold responsive neurons are functionally heterogeneous. Address for reprint requests: M. J. Caterina, Johns Hopkins School of Medicine, 725 N. Wolfe St., Baltimore, MD 21205 (E-mail: caterina{at}jhmi.edu ).