کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2198969 | 1099418 | 2009 | 8 صفحه PDF | دانلود رایگان |
Pain is a physiological state promoting protective responses to harmful episodes. However, pain can become pathophysiological and become a chronic disruptive condition, damaging quality of life. The mammalian K2P2.1 (KCNK2, TREK-1) channel, expressed in sensory neurons of the dorsal root ganglia, was previously identified as a polymodal molecular sensor involved in pain perception. Here, we report that two pain-associated signals, external acidosis and lysophosphatidic acid (LPA), known to rise during injury, inflammation and cancer, profoundly down-modulate human K2P2.1 activity. The pH regulatory effect was mediated by activation of proton-sensitive G-protein coupled receptors and phospholipase C. Physiological concentrations of LPA overcame the effects of known K2P2.1 activators, such as arachidonic acid, lysophosphatidylcholine and temperature, by activating cell-surface receptors stimulating the Gq pathway. Furthermore, we identified three K2P2.1 carboxy-terminal residues that mediate both pH and LPA regulatory effects. Our results highlight the important role of K2P2.1 channels as receptors for mediators known to cause nociception.
Journal: Molecular and Cellular Neuroscience - Volume 40, Issue 3, March 2009, Pages 382–389