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Ketamine blocks voltage-gated K+ channels and causes membrane depolarization in rat mesenteric artery myocytes

  • Cardiovascular System
  • Published:
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Abstract

Clinical doses of ketamine typically increase blood pressure, heart rate, and cardiac output. However, the precise mechanism by which ketamine produces these cardiovascular effects remains unclear. The voltage-gated K+ (KV) channel is the major regulator of resting membrane potential (E m) and vascular tone in many arteries. Therefore, we sought to evaluate the effects of ketamine on KV currents using the standard whole-cell patch clamp recordings in single myocytes, enzymatically dispersed from rat mesenteric arteries. Ketamine [(±)-racemic mixture] inhibited KV currents reversibly and concentration dependently with a K d of 566.7 ± 32.3 μM and Hill coefficient of 0.75 ± 0.03. The inhibition of KV currents by ketamine was voltage independent, and the time courses of channel activation and inactivation were little affected. The effects of ketamine on steady-state activation and inactivation curves were also minimal. Use-dependent inhibition was not observed either. S(+)-ketamine inhibited KV currents with similar potency and efficacy as the racemic mixture. The average resting E m in rat mesenteric artery myocytes was −44.1 ± 4.2 mV, and both racemic and S(+)-ketamine induced depolarization of E m (15.8 ± 3.6 and 24.3 ± 5.0 mV at 100 μM, respectively). We conclude that ketamine induces E m depolarization in vascular myocytes by blocking KV channels in a state-independent manner, which may contribute to the increased vascular tone and blood pressure produced by this drug under a clinical setting.

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Acknowledgements

This work was supported by Konkuk University in 2004.

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Authors and Affiliations

  1. Department of Anesthesiology, College of Medicine, Konkuk University, Seoul, South Korea

    Seong Hyop Kim & Nam-Sik Woo

  2. Artificial Muscle Research Center, Konkuk University, Seoul, South Korea

    Young Min Bae, Dong Jun Sung & Sang Woong Park

  3. Department of Physiology, College of Medicine, Konkuk University, 322 Danwol-dong, Choongju, 380-701, South Korea

    Young Min Bae, Dong Jun Sung, Sang Woong Park, Bokyung Kim & Sung Il Cho

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  1. Seong Hyop Kim
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Correspondence to Young Min Bae.

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Kim, S.H., Bae, Y.M., Sung, D.J. et al. Ketamine blocks voltage-gated K+ channels and causes membrane depolarization in rat mesenteric artery myocytes. Pflugers Arch - Eur J Physiol 454, 891–902 (2007). https://doi.org/10.1007/s00424-007-0240-4

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