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Effects of intracellular MgADP and acidification on the inhibition of cardiac sarcolemmal ATP-sensitive potassium channels by propofol

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Abstract

Purpose

Propofol inhibits adenosine triphosphate-sensitive potassium (KATP) channels, which may result in the blocking of ischemic preconditioning in the heart. During cardiac ischemia, sarcolemmal KATP channel activity is regulated by the increased levels of cytosolic metabolites, such as adenosine diphosphate (ADP) and protons. However, it remains unclear whether these cytosolic metabolites modulate the inhibitory action of propofol. The aim of this study was to investigate the effects of intracellular MgADP and acidification on KATP channel inhibition by propofol.

Methods

We used inside-out patch-clamp configurations to investigate the effects of propofol on the activities of recombinant cardiac sarcolemmal KATP channels, which are reassociated by expressed subunits, sulfonylurea receptor (SUR) 2A, and inwardly rectifying potassium channels (Kir6.2).

Results

In the absence of MgADP, propofol inhibited the SUR2A/Kir6.2 channel currents in a concentration-dependent manner, and an IC50 of 78 µM. Increasing the intracellular MgADP concentrations to 0.1 and 0.3 mM markedly attenuated the inhibitory potency of propofol, and shifted the IC50 to 183 and 265 µM, respectively. Moreover, decreasing the intracellular pH from 7.4 to 6.5 attenuated the inhibitory potency of propofol, and shifted the IC50 to 277 µM. In addition, propofol-induced inhibition of truncated Kir6.2ΔC36 currents, which form a functional channel without SUR2A, was not affected by an increase in intracellular MgADP. However, intracellular acidification (pH 6.5) significantly reduced the propofol sensitivity of Kir6.2ΔC36 channels.

Conclusion

Our results demonstrated that the existence of intracellular MgADP and protons attenuated the direct inhibitory potency of propofol on recombinant cardiac sarcolemmal KATP channels, via SUR2A and Kir6.2 subunits, respectively.

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Authors and Affiliations

  1. Department of Anesthesiology, Tokushima University School of Medicine, 3-18-15 Kuramoto, Tokushima, 770-8503, Japan

    Hirohide Yamada, Takashi Kawano, Katsuya Tanaka & Shuzo Oshita

  2. Department of Nutrition and Metabolism, Tokushima University School of Medicine, Tokushima, Japan

    Sonoko Yasui, Kazuaki Mawatari, Akira Takahashi & Yutaka Nakaya

Authors
  1. Hirohide Yamada
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  2. Takashi Kawano
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  3. Katsuya Tanaka
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  4. Sonoko Yasui
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  5. Kazuaki Mawatari
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  6. Akira Takahashi
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  7. Yutaka Nakaya
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  8. Shuzo Oshita
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Yamada, H., Kawano, T., Tanaka, K. et al. Effects of intracellular MgADP and acidification on the inhibition of cardiac sarcolemmal ATP-sensitive potassium channels by propofol. J Anesth 21, 472–479 (2007). https://doi.org/10.1007/s00540-007-0551-9

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  • DOI: https://doi.org/10.1007/s00540-007-0551-9

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