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
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