Arachidonic acid (AA)‐sensitive tandem pore domain K (K2P) channels in rat cerebral arteries

Abstract

K2P, a new family of K channels, has over a dozen members that are expressed in various tissues throughout the body. Very little is known about the presence and function of these channels in vascular smooth muscle cells (VSMC). Five members of the K2P family are directly activated by AA. The purpose of this study was to determine (a) if AA dilates the rat middle cerebral artery (MCA) and increases K+ currents in VSMC via a non-conventional K channel, and (b) if AA-sensitive K2P are expressed in cerebral VSMC. AA (10−5 M) dilated isolated and pressurized MCAs through a mechanism independent of endothelium. The dilation to AA was not affected by inhibiting AA metabolic pathways (cyclooxygenase, epoxygenase, or lipoxygenase). The dilation elicited by AA was not affected following inhibition of KCa, Kv, KATP, or Kir using 10 mM TEA, 3 mM 4AP, 10 uM gilbenclamide, or 100 uM Ba respectively. However, the dilations were blocked by 50 mM K indicating involvement of a K channel. AA (10−5 M) increased whole cell K+ currents in dispersed cerebral VSMC. The AA-induced currents were not affected by inhibitors of the AA metabolic pathways or blockade of conventional K channels (TEA, 4AP, glibenclamide, or Ba). RT-PCR in MCA revealed message for the AA-sensitive K2Ps, TREK-1, −2, TRAAK, THIK-1, and TWIK-2. Western blot and immunohistochemistry showed the presence of TWIK-2 and TRAAK in VSMC. We conclude that AA dilates rat middle cerebral arteries through activation of an AA-sensitive K2P channel. (NIH NS46666 & AHA 027011N)