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KMID : 0811720090130060437
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Korean Journal of Physiology & Pharmacology
2009 Volume.13 No. 6 p.437 ~ p.442
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Diclofenac, a Non-steroidal Anti-inflammatory Drug, Inhibits L-type Ca2＋ Channels in Neonatal Rat Ventricular Cardiomyocytes
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Oleg V. Yarishkin
Chung Hye-Joo
Hwang Eun-Mi
Kim Dong-Gyu
Kang Da-Won
Hong Seong-Geun
Han Jae-Hee
Kang Sang-Soo
Jeong Ho-Sang
Park Jae-Yong
Yoo Jae-Cheal
Kim Deok-Ryoung
Shin Jae-Hee-Jung
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Abstract
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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?M, diclofenac inhibited reversibly the Na＋ current and did irreversibly the L-type Ca2＋ channels-mediated inward current (IC50=12.89±0.43?M) in a dose-dependent manner. However, nifedipine, a well-known L-type channel blocker, effectively inhibited the L-type Ca2＋ currents but not the Na＋ current. Our finding may explain that diclofenac causes the CV risk by the inhibition of L-type Ca2＋ channel, leading to the impairment of E-C coupling in cardiac myocytes.
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KEYWORD
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Diclofenac, L-type Ca2＋ current, Rat cardiac myocytes, NSAID
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