徳島大学 教育・研究者情報データベース(EDB)

1. 徳島大学.大学院ヘルスバイオサイエンス研究部.神経情報医学部門.病態情報医学講座(2004年4月1日〜)
2. 徳島大学.大学院ヘルスバイオサイエンス研究部.生体システム栄養科学部門.医療栄養科学講座(2004年4月1日〜)

1. 田中 克哉([徳島大学.大学院医歯薬学研究部.医学域.医科学部門.外科系.麻酔・疼痛治療医学]/[徳島大学.病院.診療科.脳·神経·精神科])

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2. 河野 崇

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3. (英) Nakamura Akiyo

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4. (英) Nazari Hossein

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5. 川人 伸次([徳島大学.大学院医歯薬学研究部.歯学域.口腔科学部門.臨床歯学系.歯科麻酔科学])

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6. 大下 修造

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7. 髙橋 章([徳島大学.大学院医歯薬学研究部.医学域.栄養科学部門.医科栄養学系.予防環境栄養学])

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8. 中屋 豊

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(英) Isoflurane activates sarcolemmal adenosine Triphosphate-sensitive potassium channels in vascular smooth muscle cells: A role of protein kinase A

(英) Recent evidence indicates that vascular adenosine triphosphate-sensitive potassium (K(ATP)) channels in vascular smooth muscle cells are critical in the regulation of vascular tonus under both physiologic and pathophysiologic conditions. Studies of the interaction of volatile anesthetics with vascular K(ATP) channels have been limited. In the current study, the authors investigated the molecular mechanism of isoflurane's action on vascular K(ATP) channels. Electrophysiologic experiments were performed using cell-attached and inside-out patch clamp techniques to monitor native vascular K(ATP) channels, and recombinant K(ATP) channels comprised of inwardly rectifying potassium channel subunits (Kir6.1) and the sulfonylurea receptor (SUR2B). Isometric tension experiments were performed in rat thoracic aortic rings without endothelium. Application of isoflurane (0.5 mM) to the bath solution during cell-attached recordings induced a significant increase in K(ATP) channel activity, which was greatly reduced by pretreatment with a selective inhibitor of protein kinase A (PKA), Rp-cAMPS (100 microM). In inside-out patches, isoflurane did not activate K(ATP) channels. Isoflurane significantly activated wild-type recombinant SUR2B/Kir6.1 in cell-attached patches. Isoflurane-induced activation of wild-type channels was diminished in the PKA-insensitive mutant SUR2B-T633A/Kir6.1, SUR2B-S1465A/Kir6.1, and SUR2B/Kir6.1-S385A. In addition, the authors demonstrated that isoflurane-induced PKA activation was associated with isoflurane-induced decreases in isometric tension in the rat aorta. These results indicate that isoflurane activates K(ATP) channels via PKA activation. PKA-dependent vasodilation induced by isoflurane also was observed in isometric tension experiments. Analysis of expressed vascular-type K(ATP) channels suggested that PKA-mediated phosphorylation of both Kir6.1 and SUR2B subunits plays a pivotal role in isoflurane-induced vascular K(ATP) channel activation.

1. (英) ATP-Binding Cassette Transporters
2. アデノシン三リン酸(adenosine triphosphate)
3. (英) Anesthetics, Inhalation
4. (英) Animals
5. (英) Cyclic AMP-Dependent Protein Kinases
6. (英) Isoflurane
7. (英) KATP Channels
8. (英) Male
9. (英) Muscle, Smooth, Vascular
10. (英) Potassium Channels
11. (英) Potassium Channels, Inwardly Rectifying
12. (英) Rats
13. (英) Rats, Wistar
14. (英) Receptors, Drug
15. (英) Sarcolemma
16. (英) Vasodilation

1. (英) Article.Affiliation: Department of Anesthesiology, Tokushima University School of Medicine, Kuramoto, Tokushima, Japan. katsuya@clin.med.tokushima-u.ac.jp

2. (英) Article.PublicationTypeList.PublicationType: Journal Article

3. (英) Article.PublicationTypeList.PublicationType: Research Support, Non-U.S. Gov't