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. 河野 崇

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2. 大下 修造

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3. 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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4. (英) Tsutsumi Yasuo / (日) 堤 保夫 / (読) つつみ やすお

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5. 富山 芳信([徳島大学.病院.中央診療施設等.手術部])

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6. 北畑 洋

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7. 黒田 泰弘

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8. 中屋 豊

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(英) Molecular Mechanisms of the Inhibitory Effects of Bupivacaine, Levobupivacaine, and Ropivacaine on Sarcolemmal Adenosine Triphosphate-sensitive Potassium Channels in the Cardiovascular System.

(英) Sarcolemmal adenosine triphosphate-sensitive potassium (KATP) channels in the cardiovascular system may be involved in bupivacaine-induced cardiovascular toxicity. The authors investigated the effects of local anesthetics on the activity of reconstituted KATP channels encoded by inwardly rectifying potassium channel (Kir6.0) and sulfonylurea receptor (SUR) subunits. The authors used an inside-out patch clamp configuration to investigate the effects of bupivacaine, levobupivacaine, and ropivacaine on the activity of reconstituted KATP channels expressed in COS-7 cells and containing wild-type, mutant, or chimeric SURs. Bupivacaine inhibited the activities of cardiac KATP channels (IC50 = 52 microm) stereoselectively (levobupivacaine, IC50 = 168 microm; ropivacaine, IC50 = 249 microm). Local anesthetics also inhibited the activities of channels formed by the truncated isoform of Kir6.2 (Kir6.2 delta C36) stereoselectively. Mutations in the cytosolic end of the second transmembrane domain of Kir6.2 markedly decreased both the local anesthetics' affinity and stereoselectivity. The local anesthetics blocked cardiac KATP channels with approximately eightfold higher potency than vascular KATP channels; the potency depended on the SUR subtype. The 42 amino acid residues at the C-terminal tail of SUR2A, but not SUR1 or SUR2B, enhanced the inhibitory effect of bupivacaine on the Kir6.0 subunit. Inhibitory effects of local anesthetics on KATP channels in the cardiovascular system are (1) stereoselective: bupivacaine was more potent than levobupivacaine and ropivacaine; and (2) tissue specific: local anesthetics blocked cardiac KATP channels more potently than vascular KATP channels, via the intracellular pore mouth of the Kir6.0 subunit and the 42 amino acids at the C-terminal tail of the SUR2A subunit, respectively.

1. (英) ATP-Binding Cassette Transporters
2. (英) Algorithms
3. (英) Amides
4. (英) Anesthetics, Local
5. (英) Animals
6. (英) Bupivacaine
7. (英) COS Cells
8. (英) Cercopithecus aethiops
9. (英) Dose-Response Relationship, Drug
10. (英) Membrane Potentials
11. (英) Membrane Proteins
12. (英) Patch-Clamp Techniques
13. (英) Potassium Channel Blockers
14. (英) Potassium Channels
15. (英) Potassium Channels, Inwardly Rectifying
16. (英) Receptors, Drug
17. (英) Stereoisomerism
18. (英) Sulfonylurea Compounds
19. (英) Transfection

1. (英) Article.Affiliation: Department of Anesthesiology, Tokushima University School of Medicine, Kuramoto, Tokushima, 770-8503, Japan. haf26740@ams.odn.ne.jp

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

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