Evidence for two-pore domain potassium channels in rat cerebral arteries

被引:45
作者
Bryan, Robert M., Jr.
You, Junping
Phillips, Sharon C.
Andresen, Jon J.
Lloyd, Eric E.
Rogers, Paul A.
Dryer, Stuart E.
Marrelli, Sean P.
机构
[1] Baylor Coll Med, Dept Anesthesiol, Houston, TX 77030 USA
[2] Baylor Coll Med, Dept Med Cardiovasc Sci, Houston, TX 77030 USA
[3] Baylor Coll Med, Dept Mol Physiol & Biophys, Houston, TX 77030 USA
[4] Univ Houston, Dept Biochem & Biol Sci, Houston, TX 77004 USA
[5] Louisiana State Univ, Hlth Sci Ctr, Dept Physiol, New Orleans, LA 70112 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY | 2006年 / 291卷 / 02期
关键词
arachidonic acid; arachidonic acid-stimulated potassium channel; membrane potential; hyperpolarization; vasodilation; electrophysiology; TREK-1; TREK-2; TRAAK; THIK-1; TWIK-2;
D O I
10.1152/ajpheart.01377.2005
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Little is known about the presence and function of two-pore domain K+ (K-2P) channels in vascular smooth muscle cells (VSMCs). Five members of the K-2P channel family are known to be directly activated by arachidonic acid (AA). The purpose of this study was to determine 1) whether AA-sensitive K2P channels are expressed in cerebral VSMCs and 2) whether AA dilates the rat middle cerebral artery (MCA) by increasing K+ currents in VSMCs via an atypical K+ channel. RT-PCR revealed message for the following AA-sensitive K-2P channels in rat MCA: tandem of P domains in weak inward rectifier K+ (TWIK-2), TWIK-related K+ (TREK-1 and TREK-2), TWIK-related AA-stimulated K+ (TRAAK), and TWIK-related halothane-inhibited K+ (THIK-1) channels. However, in isolated VSMCs, only message for TWIK-2 was found. Western blotting showed that TWIK-2 is present in MCA, and immunohistochemistry further demonstrated its presence in VSMCs. AA (10 - 100 mu M) dilated MCAs through an endotheliumin-dependent mechanism. AA-induced dilation was not affected by inhibition of cyclooxygenase, epoxygenase, or lipoxygenase or inhibition of classical K+ channels with 10 mM TEA, 3 mM 4-aminopyridine, 10 mu M glibenclamide, or 100 mu M Ba2+. AA-induced dilations were blocked by 50 mM K+, indicating involvement of a K+ channel. AA (10 mu M) increased whole cell K+ currents in dispersed cerebral VSMCs. AA-induced currents were not affected by inhibitors of the AA metabolic pathways or blockade of classical K+ channels. We conclude that AA dilates the rat MCA and increases K+ currents in VSMCs via an atypical K+ channel that is likely a member of the K-2P channel family.
引用
收藏
页码:H770 / H780
页数:11
相关论文
共 45 条
[21]   Synergistic interaction and the rose of C-terminus in the activation of TRAAK K+ channels by pressure, free fatty acids and alkali [J].
Kim, Y ;
Bang, H ;
Gnatenco, C ;
Kim, D .
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 2001, 442 (01) :64-72
[22]   TREK-1 regulation by nitric oxide and cGMP-dependent protein kinase - An essential role in smooth muscle inhibitory neurotransmission [J].
Koh, SD ;
Monaghan, K ;
Sergeant, GP ;
Ro, S ;
Walker, RL ;
Sanders, KM ;
Horowitz, B .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (47) :44338-44346
[23]  
Köhler R, 2000, CIRC RES, V87, P496
[24]   OXYGEN RADICALS MEDIATE THE CEREBRAL ARTERIOLAR DILATION FROM ARACHIDONATE AND BRADYKININ IN CATS [J].
KONTOS, HA ;
WEI, EP ;
POVLISHOCK, JT ;
CHRISTMAN, CW .
CIRCULATION RESEARCH, 1984, 55 (03) :295-303
[25]   Molecular and functional properties of two-pore-domain potassium channels [J].
Lesage, F ;
Lazdunski, M .
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, 2000, 279 (05) :F793-F801
[26]   Human TREK2, a 2P domain mechano-sensitive K+ channel with multiple regulations by polyunsaturated fatty acids, lysophospholipids, and Gs, Gi, and Gq protein-coupled receptors [J].
Lesage, F ;
Terrenoire, C ;
Romey, G ;
Lazdunski, M .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (37) :28398-28405
[27]   Cloning and expression of human TRAAK, a polyunsaturated fatty acids-activated and mechano-sensitive K+ channel [J].
Lesage, F ;
Maingret, F ;
Lazdunski, M .
FEBS LETTERS, 2000, 471 (2-3) :137-140
[28]   Pharmacology of neuronal background potassium channels [J].
Lesage, F .
NEUROPHARMACOLOGY, 2003, 44 (01) :1-7
[29]   PIP2 hydrolysis underlies agonist-induced inhibition and regulates voltage gating of two-pore domain K+ channels [J].
Lopes, CMB ;
Rohács, T ;
Czirják, G ;
Balla, T ;
Enyedi, P ;
Logothetis, DE .
JOURNAL OF PHYSIOLOGY-LONDON, 2005, 564 (01) :117-129
[30]   TREK-1 is a heat-activated background K+ channel [J].
Maingret, F ;
Lauritzen, I ;
Patel, AJ ;
Heurteaux, C ;
Reyes, R ;
Lesage, F ;
Lazdunski, M ;
Honoré, E .
EMBO JOURNAL, 2000, 19 (11) :2483-2491