L-cis Diltiazem attenuates intracellular Ca2+ overload by metabolic inhibition in guinea pig myocytes

Motohiro Nishida, Tetsuro Urushidani, Kenji Sakamoto, Taku Nagao

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Abstract

We have previously demonstrated that treatment with L-cis diltiazem reduced cardiac infarct size in vivo. To examine the effect of L-cis diltiazem on Ca2+ overload induced by ischemia/reperfusion, we used a model for Ca2+ overload produced by metabolic inhibition in isolated guinea pig myocytes. Intracellular Ca2+ concentration ([Ca2+](i)) was quantified by fura-2 fluorescence microscopy and Ca2+ overload was induced by inclusion of 1 μM of carbonyl cyanide m-chrolophenylhydrazone (CCCP) for 40 min treatment followed by washout for 30 min. This treatment caused a large [Ca2+](i) elevation as well as a sustained contracture of the cardiomyocytes. The increase was suppressed by 10 μM of 2-[2-[4-(4-nitrobenzyloxy) phenyl] ethyl] isothiourea methanesulphonate (KB-R7943), a specific inhibitor of the Na+/Ca2+ exchanger, but not by nitrendipine (10 μM). L-cis Diltiazem (10 μM) attenuated the [Ca2+](i) increase, suggesting that L-cis diltiazem elicits a cardioprotective effect via attenuation of the [Ca2+](i) increase induced by metabolic inhibition and energy repletion. Copyright (C) 1999 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)225-230
Number of pages6
JournalEuropean Journal of Pharmacology
Volume385
Issue number2-3
DOIs
Publication statusPublished - Dec 3 1999
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Pharmacology

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