Pharmacological Blockade of TRPM8 Ion Channels Alters Cold and Cold Pain Responses in Mice

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Pharmacological Blockade of TRPM8 Ion Channels Alters Cold and Cold Pain Responses in Mice

TRPM8 (Transient Receptor Potential Melastatin-8) is a cold- and menthol-gated ion channel necessary for the detection of cold temperatures in the mammalian peripheral nervous system. Functioning TRPM8 channels are required for behavioral responses to innocuous cool, noxious cold, injury-evoked cold hypersensitivity, cooling-mediated analgesia, and thermoregulation. Because of these various rol...

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Voltage- and cold-dependent gating of single TRPM8 ion channels

Transient receptor potential (TRP) channels play critical roles in cell signaling by coupling various environmental factors to changes in membrane potential that modulate calcium influx. TRP channels are typically activated in a polymodal manner, thus integrating multiple stimuli. Although much progress has been made, the underlying mechanisms of TRP channel activation are largely unknown. The ...

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Pharmacological blockade of the cold receptor TRPM8 attenuates autonomic and behavioral cold defenses and decreases deep body temperature.

We studied N-(2-aminoethyl)-N-(4-(benzyloxy)-3-methoxybenzyl)thiophene-2-carboxamide hydrochloride (M8-B), a selective and potent antagonist of the transient receptor potential melastatin-8 (TRPM8) channel. In vitro, M8-B blocked cold-induced and TRPM8-agonist-induced activation of rat, human, and murine TRPM8 channels, including those on primary sensory neurons. In vivo, M8-B decreased deep bo...

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Attenuated Cold Sensitivity in TRPM8 Null Mice

Thermosensation is an essential sensory function that is subserved by a variety of transducer molecules, including those from the Transient Receptor Potential (TRP) ion channel superfamily. One of its members, TRPM8 (CMR1), a ligand-gated, nonselective cation channel, is activated by both cold and chemical stimuli in vitro. However, its roles in cold thermosensation and pain in vivo have not be...

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Structure of the cold- and menthol-sensing ion channel TRPM8.

Transient receptor potential melastatin (TRPM) cation channels are polymodal sensors that are involved in a variety of physiological processes. Within the TRPM family, member 8 (TRPM8) is the primary cold and menthol sensor in humans. We determined the cryo-electron microscopy structure of the full-length TRPM8 from the collared flycatcher at an overall resolution of ~4.1 ångstroms. Our TRPM8 s...

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ژورنال

عنوان ژورنال: PLoS ONE

سال: 2011

ISSN: 1932-6203

DOI: 10.1371/journal.pone.0025894