Diclofenac, a Non-steroidal Anti-inflammatory Drug, Inhibits L-type Ca2＋ Channels in Neonatal Rat Ventricular Cardiomyocytes

• 영문명: Diclofenac, a Non-steroidal Anti-inflammatory Drug, Inhibits L-type Ca^2＋ Channels in Neonatal Rat Ventricular Cardiomyocytes
• 발행기관: 대한생리학회-대한약리학회
• 저자명: Oleg V. Yarishkin Eun Mi Hwang Donggyu Kim Jae Cheal Yoo Sang Soo Kang Deok Ryoung Kim Jae-Hee-Jung
• 간행물 정보: 『The Korean Journal of Physiology & Pharmacology』제13권 제6호, 437~442쪽, 전체 6쪽
• 주제분류: 의약학 > 의학일반
• 파일형태: PDF
• 발행일자: 2009.01.01

영문 초록

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 3ՌM, diclofenac inhibited reversibly the Na^＋ current and did irreversibly the L-type Ca^2＋ channels-mediated inward current (IC₅₀=12.89±0.43ՌM) 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.

키워드

Diclofenac L-type Ca^2＋ current Rat cardiac myocytes NSAID