Differential Effects of Etomidate and Midazolam on Vascular Adenosine Triphosphate–sensitive Potassium Channels

• Akiyo Nakamura

  Graduate Student.

• Shinji Kawahito

  Assistant Professor.

• Takashi Kawano

  Instructor.

• Hossein Nazari

  Graduate Student, Division of Molecular Genetics, Institute for Enzyme Research, University of Tokushima, Tokushima, Japan.

• Akira Takahashi

  Associate Professor.

• Hiroshi Kitahata

  Associate Professor.

• Yutaka Nakaya

  Professor and Chairman, Department of Nutrition and Metabolism, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan.

• Shuzo Oshita

  Professor and Chairman, Department of Anesthesiology.

抄録

The aim of this study was to investigate the effects of two imidazoline-derived intravenous anesthetics, etomidate and midazolam, on vascular adenosine triphosphate-sensitive potassium (KATP) channel activity. In isolated rat aorta, isometric tension was recorded to examine the anesthetic effects on vasodilator response to levcromakalim, a selective KATP channel opener. Using the patch clamp method, the anesthetic effects were also examined on the currents through (1) native vascular KATP channels, (2) recombinant KATP channels with different combinations of various types of inwardly rectifying potassium channel (Kir6.0 family: Kir6.1, 6.2) and sulfonylurea receptor (SUR1, 2A, 2B) subunits, (3) SUR-deficient channels derived from a truncated isoform of Kir6.2 subunit (Kir6.2DeltaC36 channels), and (4) mutant Kir6.2DeltaC36 channels with reduced sensitivity to adenosine triphosphate (Kir6.2DeltaC36-K185Q channels). Etomidate (> or = 10 m), but not midazolam (up to 10 m), inhibited the levcromakalim-induced vasodilation, which was sensitive to glibenclamide (IC50: 7.21 x 10 m; maximum inhibitory concentration: 1.22 x 10 m). Etomidate (> or = 3 x 10 m), but not midazolam (up to 10 m), inhibited the native KATP channel activity in both cell-attached and inside-out configurations with IC50 values of 1.68 x 10 m and 1.52 x 10 m, respectively. Etomidate (10 m) also inhibited the activity of various types of recombinant SUR/Kir6.0KATP channels, Kir6.2DeltaC36 channels, and Kir6.2DeltaC36-K185Q channels with equivalent potency. Clinical concentrations of etomidate, but not midazolam, inhibit the KATP channel activity in vascular smooth muscle cells. The inhibition is presumably through its effects on the Kir6.0 subunit, but not on the SUR subunit, with the binding site different from adenosine triphosphate at the amino acid level.

収録刊行物

• Anesthesiology

  Anesthesiology 106 (3), 515-522, 2007-03-01

  Ovid Technologies (Wolters Kluwer Health)

キーワード

• Anesthesiology and Pain Medicine

詳細情報

• CRID: 1362544421350056576
• NII論文ID: 30025690842
• DOI: 10.1097/00000542-200703000-00016
• ISSN: 00033022
• Web Site: http://pubs.asahq.org/anesthesiology/article-pdf/106/3/515/363804/0000542-200703000-00016.pdf
• Web Site: http://journals.lww.com/00000542-200703000-00016
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