Lamotrigine inhibits TRESK regulated by G-protein coupled receptor agonists.
Dorsal root ganglion (DRG) neurons express mRNAs for numerous two-pore domain K(+) (K(2P)) 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 microM lamotrigine inhibited TRESK by approximately 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.
Kang
Dawon
D
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.
Kim
Gyu-Tae
GT
Kim
Eun-Jin
EJ
La
Jun-Ho
JH
Lee
Jeong-Soon
JS
Lee
Eun-Shin
ES
Park
Jae-Yong
JY
Hong
Seong-Geun
SG
Han
Jaehee
J
D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D019556:COS Cells; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D004305:Dose-Response Relationship, Drug; D005473:Fluoxetine / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018698:Glutamic Acid / Q000494:pharmacology; D000077213:Lamotrigine; D051379:Mice; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000378:metabolism; D014227:Triazines / Q000494:pharmacology*
D000700:Analgesics; D005473:Fluoxetine; D018698:Glutamic Acid; D000077213:Lamotrigine; D015221:Potassium Channels; D043562:Receptors, G-Protein-Coupled; D014227:Triazines; C486498:Kcnk18 protein, mouse