Abstract
Pirt is a membrane protein that is specifically expressed in the peripheral nervous system, where it has been shown to increase the sensitivity of the transient receptor potential vanilloid 1 channel and modulate its role in heat pain. The broad expression of Pirt among dorsal root ganglion neurons suggests it may modulate other transient receptor potentials, such as the menthol and cooling sensor TRPM8. The discrepancies in the channel properties of TRPM8 in native neurons versus heterologous cells indicate the existence of endogenous modulators of the channel. Here we show that Pirt regulates the function of TRPM8 and its role in detecting cold. Pirt(-/-) mice exhibit decreased behavioural responses to cold and cool temperatures, and Pirt increases the sensitivity of TRPM8 to menthol and cool temperature. Our data suggest Pirt is an endogenous regulator of TRPM8.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Animals
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Behavior, Animal
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Calcium / metabolism
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Carrier Proteins / genetics*
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Cold Temperature
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Evoked Potentials, Somatosensory / physiology
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Ganglia, Spinal / cytology
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Ganglia, Spinal / drug effects
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Ganglia, Spinal / physiology*
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Gene Expression Regulation
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HEK293 Cells
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Humans
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Male
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Membrane Proteins / deficiency
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Membrane Proteins / genetics*
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Menthol / pharmacology
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Mice
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Mice, Knockout
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Neurons, Afferent / cytology
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Neurons, Afferent / drug effects
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Neurons, Afferent / physiology*
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Olfactory Perception / physiology*
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Pain Perception / physiology*
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Signal Transduction
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TRPM Cation Channels / genetics*
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TRPM Cation Channels / metabolism
Substances
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Carrier Proteins
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Membrane Proteins
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Pirt protein, mouse
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TRPM Cation Channels
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TRPM8 protein, mouse
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Menthol
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Calcium