title: Diclofenac, a Non-steroidal Anti-inflammatory Drug, Inhibits L-type Ca Channels in Neonatal Rat Ventricular Cardiomyocytes.
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 microM, diclofenac inhibited reversibly the Na(+) current and did irreversibly the L-type Ca(2+) channels-mediated inward current (IC(50)=12.89+/-0.43 microM) 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.
authors.affiliation: Department of Physiology, Institute of Health Sciences, and Medical Research Center for Neural Dysfunction, Gyeongsang National University School of Medicine, Jinju 660-751, Korea.
authors.forename: Oleg V
authors.initials: OV
authors.lastname: Yarishkin
authors.forename: Eun Mi
authors.initials: EM
authors.lastname: Hwang
authors.forename: Donggyu
authors.initials: D
authors.lastname: Kim
authors.forename: Jae Cheal
authors.initials: JC
authors.lastname: Yoo
authors.forename: Sang Soo
authors.initials: SS
authors.lastname: Kang
authors.forename: Deok Ryoung
authors.initials: DR
authors.lastname: Kim
authors.forename: Jae-Hee-Jung
authors.initials: JH
authors.lastname: Shin
authors.forename: Hye-Joo
authors.initials: HJ
authors.lastname: Chung
authors.forename: Ho-Sang
authors.initials: HS
authors.lastname: Jeong
authors.forename: Dawon
authors.initials: D
authors.lastname: Kang
authors.forename: Jaehee
authors.initials: J
authors.lastname: Han
authors.forename: Jae-Yong
authors.initials: JY
authors.lastname: Park
authors.forename: Seong-Geun
authors.initials: SG
authors.lastname: Hong