The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Diclofenac, a Non-steroidal Anti-inflammatory Drug, Inhibits L-type $Ca^{2+}$ Channels in Neonatal Rat Ventricular Cardiomyocytes

  • Yarishkin, Oleg V. (Department of Physiology, Institute of Health Sciences, and Medical Research Center for Neural Dysfunction, Gyeongsang National University School of Medicine) ;
  • Hwang, Eun-Mi (Department of Physiology, Institute of Health Sciences, and Medical Research Center for Neural Dysfunction, Gyeongsang National University School of Medicine) ;
  • Kim, Dong-Gyu (Department of Physiology, Institute of Health Sciences, and Medical Research Center for Neural Dysfunction, Gyeongsang National University School of Medicine) ;
  • Yoo, Jae-Cheal (Department of Physiology, Institute of Health Sciences, and Medical Research Center for Neural Dysfunction, Gyeongsang National University School of Medicine) ;
  • Kang, Sang-Soo (Department of Anatomy, Institute of Health Sciences, and Medical Research Center for Neural Dysfunction, Gyeongsang National University School of Medicine) ;
  • Kim, Deok-Ryoung (Department of Biochemistry, Institute of Health Sciences, and Medical Research Center for Neural Dysfunction, Gyeongsang National University School of Medicine) ;
  • Shin, Jae-Hee-Jung (Division of Molecular Pharmacology, National Institute of Toxicological Research, Korea Food and Drug Administration) ;
  • Chung, Hye-Joo (Division of Molecular Pharmacology, National Institute of Toxicological Research, Korea Food and Drug Administration) ;
  • Jeong, Ho-Sang (Division of Molecular Pharmacology, National Institute of Toxicological Research, Korea Food and Drug Administration) ;
  • Kang, Da-Won (Department of Physiology, Institute of Health Sciences, and Medical Research Center for Neural Dysfunction, Gyeongsang National University School of Medicine) ;
  • Han, Jae-Hee (Department of Physiology, Institute of Health Sciences, and Medical Research Center for Neural Dysfunction, Gyeongsang National University School of Medicine) ;
  • Park, Jae-Yong (Department of Physiology, Institute of Health Sciences, and Medical Research Center for Neural Dysfunction, Gyeongsang National University School of Medicine) ;
  • Hong, Seong-Geun (Department of Physiology, Institute of Health Sciences, and Medical Research Center for Neural Dysfunction, Gyeongsang National University School of Medicine)
  • Published : 2009.12.31
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Abstract

A non-steroidal anti-inflammatory drug (NSAID) has many adverse effects including cardiovascular (CV) risk. Diclofenac among the nonselective NSAIDs has the highest CV risk such as congestive heart failure, which resulted commonly from the impaired cardiac pumping due to a disrupted excitationcontraction (E-C) coupling. We investigated the effects of diclofenac on the L-type calcium channels which are essential to the E-C coupling at the level of single ventricular myocytes isolated from neonatal rat heart, using the whole-cell voltage-clamp technique. Only diclofenac of three NSAIDs, including naproxen and ibuprofen, significantly reduced inward whole cell currents. At concentrations higher than $3\;{\mu}M$, diclofenac inhibited reversibly the $Na^+$ current and did irreversibly the L-type $Ca^{2+}$ channels-mediated inward current $(IC_{50}=12.89\pm0.43\;{\mu}M)$ in a dose-dependent manner. However, nifedipine, a well-known L-type channel blocker, effectively inhibited the L-type $Ca^{2+}$ currents but not the $Na^+$ current. Our finding may explain that diclofenac causes the CV risk by the inhibition of L-type $Ca^{2+}$ channel, leading to the impairment of E-C coupling in cardiac myocytes.

Keywords

References

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