K ATP channels in pig and human intracranial arteries

• Published in: European journal of pharmacology 2008-12, Vol.601 (1), p.43-49
• Main Authors: Ploug, Kenneth Beri, Sørensen, Mette Aaskov, Strøbech, Lotte, Klaerke, Dan Arne, Hay-Schmidt, Anders, Sheykhzade, Majid, Olesen, Jes, Jansen-Olesen, Inger
• Format: Article
• Language: English
• Subjects: Adamantane - analogs & derivatives; Adamantane - pharmacology; Animals; ATP-Binding Cassette Transporters - metabolism; Cerebral Arteries - metabolism; Gene Expression; Humans; in vitro studies; K ATP channel (ATP-sensitive K + channel); KATP Channels - metabolism; Male; MCA (middle cerebral artery); Meningeal Arteries - metabolism; Middle Aged; MMA (middle meningeal artery); Morpholines - pharmacology; mRNA expression studies; Potassium Channel Blockers - pharmacology; Potassium Channels, Inwardly Rectifying - metabolism; Receptors, Drug - metabolism; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - metabolism; Species Specificity; Sulfonylurea Receptors; Swine
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2008.10.041

Clinical trials suggest that synthetic ATP-sensitive K + (K ATP) channel openers may cause headache and migraine by dilating cerebral and meningeal arteries. We studied the mRNA expression profile of K ATP channel subunits in the pig and human middle meningeal artery (MMA) and in the pig middle cerebral artery (MCA). We determined the order of potency of four K ATP channel openers when applied to isolated pig MMA and MCA, and we examined the potential inhibitory effects of the Kir6.1 subunit specific K ATP channel blocker PNU-37883A on K ATP channel opener-induced relaxation of the isolated pig MMA and MCA. Using conventional RT-PCR, we detected the mRNA transcripts of the K ATP channel subunits Kir6.1 and SUR2B in all the examined pig and human intracranial arteries. Application of K ATP channel openers to isolated pig MMA and MCA in myographs caused a concentration-dependent vasodilatation with an order of potency that supports the presence of functional SUR2B K ATP channel subunits. 10 − 7  M PNU-37883A significantly inhibited the in vitro dilatory responses of the potent K ATP channel opener P-1075 in both pig MMA and MCA. In conclusion, our combined mRNA expression and pharmacological studies indicate that Kir6.1/SUR2B is the major functional K ATP channel complex in the pig MMA and MCA, and mRNA expression studies suggest that the human MMA shares this K ATP channel subunit profile. Specific blocking of Kir6.1 or SUR2B K ATP channel subunits in large cerebral and meningeal arteries may be a future anti-migraine strategy.