Lamotrigine inhibits TRESK regulated by G-protein coupled receptor agonists |
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Authors: | Kang Dawon Kim Gyu-Tae Kim Eun-Jin La Jun-Ho Lee Jeong-Soon Lee Eun-Shin Park Jae-Yong Hong Seong-Geun Han Jaehee |
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Affiliation: | a Medical Research Center for Neural Dysfunction and Department of Physiology, College of Medicine and Institute of Health Sciences, Gyeongsang National University, 90 Chilam, Jinju 660-751, South Korea b Department of Rehabilitation Medicine, College of Medicine and Institute of Health Sciences, Gyeongsang National University, Jinju 660-751, South Korea |
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Abstract: | Dorsal root ganglion (DRG) neurons express mRNAs for numerous two-pore domain K+ (K2P) channels and G-protein coupled receptors (GPCR). Recent studies have shown that TRESK is a major background K+ channel in DRG neurons. Here, we demonstrate the pharmacological properties of TRESK, including GPCR agonist-induced effects on DRG neurons. TRESK mRNA was highly expressed in DRG compared to brain and spinal cord. Similar to cloned TRESK, native TRESK was inhibited by acid and arachidonic acid (AA), but not zinc. Native TRESK was also activated by GPCR agonists such as acetylcholine, glutamate, and histamine. The glutamate-activated TRESK was blocked by lamotrigine in DRG neurons. In COS-7 cells transfected with mouse TRESK, 30 μM lamotrigine inhibited TRESK by ∼50%. Since TRESK is target of modulation by acid, AA, GPCR agonists, and lamotrigine, it is likely to play an active role in the regulation of excitability in DRG neurons. |
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Keywords: | Tandem-pore domain potassium channel Ganglia G-protein coupled receptor Lamotrigine |
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