Journal
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
Volume 291, Issue 2, Pages H770-H780Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpheart.01377.2005
Keywords
arachidonic acid; arachidonic acid-stimulated potassium channel; membrane potential; hyperpolarization; vasodilation; electrophysiology; TREK-1; TREK-2; TRAAK; THIK-1; TWIK-2
Funding
- NHLBI NIH HHS [F32 HL-080916] Funding Source: Medline
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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.
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