Diclofenac, a non-steroidal anti-inflammatory drug, inhibits L-type Ca 2+ channels in neonatal rat ventricular cardiomyocytes

Oleg V. Yarishkin, Eun Mi Hwang, Donggyu Kim, Jae Cheal Yoo, Sang Soo Kang, Deok Ryoung Kim, Jae Hee Jung Shin, Hye Joo Chung, Ho Sang Jeong, Dawon Kang, Jaehee Han, Jae-Yong Park, Seong Geun Hong

Research output: Contribution to journalArticle

16 Citations (Scopus)

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 excitation-contraction (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 μM, diclofenac inhibited reversibly the Na + current and did irreversibly the L-type Ca 2+ channels-mediated inward current (IC 50 =12.89±0.43 μM) 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.

Original languageEnglish
Pages (from-to)437-442
Number of pages6
JournalKorean Journal of Physiology and Pharmacology
Volume13
Issue number6
DOIs
Publication statusPublished - 2009 Dec 1
Externally publishedYes

Fingerprint

Diclofenac
Cardiac Myocytes
Anti-Inflammatory Agents
Excitation Contraction Coupling
Pharmaceutical Preparations
Non-Steroidal Anti-Inflammatory Agents
L-Type Calcium Channels
Naproxen
Ibuprofen
Patch-Clamp Techniques
Nifedipine
Muscle Cells
Heart Failure

Keywords

  • Diclofenac
  • L-type Ca current
  • NSAID
  • Rat cardiac myocytes

ASJC Scopus subject areas

  • Physiology
  • Pharmacology

Cite this

Diclofenac, a non-steroidal anti-inflammatory drug, inhibits L-type Ca 2+ channels in neonatal rat ventricular cardiomyocytes . / Yarishkin, Oleg V.; Hwang, Eun Mi; Kim, Donggyu; Yoo, Jae Cheal; Kang, Sang Soo; Kim, Deok Ryoung; Shin, Jae Hee Jung; Chung, Hye Joo; Jeong, Ho Sang; Kang, Dawon; Han, Jaehee; Park, Jae-Yong; Hong, Seong Geun.

In: Korean Journal of Physiology and Pharmacology, Vol. 13, No. 6, 01.12.2009, p. 437-442.

Research output: Contribution to journalArticle

Yarishkin, OV, Hwang, EM, Kim, D, Yoo, JC, Kang, SS, Kim, DR, Shin, JHJ, Chung, HJ, Jeong, HS, Kang, D, Han, J, Park, J-Y & Hong, SG 2009, ' Diclofenac, a non-steroidal anti-inflammatory drug, inhibits L-type Ca 2+ channels in neonatal rat ventricular cardiomyocytes ', Korean Journal of Physiology and Pharmacology, vol. 13, no. 6, pp. 437-442. https://doi.org/10.4196/kjpp.2009.13.6.437
Yarishkin, Oleg V. ; Hwang, Eun Mi ; Kim, Donggyu ; Yoo, Jae Cheal ; Kang, Sang Soo ; Kim, Deok Ryoung ; Shin, Jae Hee Jung ; Chung, Hye Joo ; Jeong, Ho Sang ; Kang, Dawon ; Han, Jaehee ; Park, Jae-Yong ; Hong, Seong Geun. / Diclofenac, a non-steroidal anti-inflammatory drug, inhibits L-type Ca 2+ channels in neonatal rat ventricular cardiomyocytes In: Korean Journal of Physiology and Pharmacology. 2009 ; Vol. 13, No. 6. pp. 437-442.
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