Gating of Transient Receptor Potential Melastatin 8 (TRPM8) Channels Activated by Cold and Chemical Agonists in Planar Lipid Bilayers

• DOI: 10.1523/jneurosci.3189-10.2010
• Publication Date: 2010-09-15T16:44:02Z
• Authors: Eleonora Zakharian; Chike Cao; Tibor Rohacs
• Keywords: TRPM8

The transient receptor potential melastatin 8 (TRPM8) ion channel is a major sensor of environmental cold temperatures. It activated by and chemical agonists, such as menthol icilin. activation these channels both cooling agents requires the presence membrane phospholipid phosphatidylinositol 4,5-bisphosphate [PI(4,5)P 2 ]. mechanism TRPM8 physical factors unknown, involvement cellular signaling pathways has been considered. Here we have characterized gating rat reconstituted in planar lipid bilayers its different stimuli. In this system, influence can be excluded. We found that exhibits steep temperature dependence [temperature coefficient ( Q 10 ) ∼40], openings are accompanied large changes entropy enthalpy, suggesting substantial conformation change. behavior upon icilin was distinguishable, effect depended on calcium intracellular side protein. also demonstrate PI(4,5)P prime factor impacts other phosphoinositides less efficient supporting activity. Menthol increases potency to activate binding full-length Our data conclusively gated agonists directly, result direct specific interactions with lipid.