TY - JOUR
T1 - Lamotrigine inhibits TRESK regulated by G-protein coupled receptor agonists
AU - Kang, Dawon
AU - Kim, Gyu Tae
AU - Kim, Eun Jin
AU - La, Jun Ho
AU - Lee, Jeong Soon
AU - Lee, Eun Shin
AU - Park, Jae Yong
AU - Hong, Seong Geun
AU - Han, Jaehee
N1 - Funding Information:
This work was supported by the Korea Research Foundation Grant funded by the Korean Government (KRF-2006-11-E00158, KRF-2006-005-J04204), and partially supported by the Basic Research Program of the KOSEF (R13-2005-012-01002-0).
Copyright:
Copyright 2009 Elsevier B.V., All rights reserved.
PY - 2008/3/14
Y1 - 2008/3/14
N2 - 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.
AB - 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.
KW - G-protein coupled receptor
KW - Ganglia
KW - Lamotrigine
KW - Tandem-pore domain potassium channel
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U2 - 10.1016/j.bbrc.2008.01.008
DO - 10.1016/j.bbrc.2008.01.008
M3 - Article
C2 - 18190784
AN - SCOPUS:38749093319
VL - 367
SP - 609
EP - 615
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 3
ER -