Journal
JOURNAL OF NEUROSCIENCE
Volume 29, Issue 10, Pages 3120-3131Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.4778-08.2009
Keywords
-
Categories
Funding
- Spanish Ministry of Education and Science [BFU2007-61855, BFU2005-08741]
- CONSOLIDER-INGENIO 2010 [CSD2007-00023]
- Spanish Fundacion Marcelino Botin
Ask authors/readers for more resources
Molecular determinants of threshold differences among cold thermoreceptors are unknown. Here we show that such differences correlate with the relative expression of I-KD, a current dependent on Shaker-like Kv1 channels that acts as an excitability brake, and I-TRPM8, a cold-activated excitatory current. Neurons responding to small temperature changes have high functional expression of TRPM8 (transient receptor potential cation channel, subfamily M, member 8) and low expression of IKD. In contrast, neurons activated by lower temperatures have a lower expression of TRPM8 and a prominent IKD. Otherwise, both subpopulations have nearly identical membrane and firing properties, suggesting that they belong to the same neuronal pool. Blockade of IKD shifts the threshold of cold-sensitive neurons to higher temperatures and augments cold-evoked nocifensive responses in mice. Similar behavioral effects of IKD blockade were observed in TRPA1(-/-) mice. Moreover, only a small percentage of trigeminal cold-sensitive neurons were activated by TRPA1 agonists, suggesting that TRPA1 does not play a major role in the detection of low temperatures by uninjured somatic cold-specific thermosensory neurons under physiological conditions. Collectively, these findings suggest that innocuous cooling sensations and cold discomfort are signaled by specific low- and high-threshold cold thermoreceptor neurons, differing primarily in their relative expression of two ion channels having antagonistic effects on neuronal excitability. Thus, although TRPM8 appears to function as a critical cold sensor in the majority of peripheral sensory neurons, the expression of Kv1 channels in the same terminals seem to play an important role in the peripheral gating of cold-evoked discomfort and pain.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available