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Title:PLATELET ACTIVATING FACTOR AFFECTS INTRACELLULAR CALCIUM CONCENTRATION BY MODULATING L-TYPE CALCIUM CHANNEL
DOI No:10.1142/9789812702234_0022
Source:ADVANCES IN ELECTROCARDIOLOGY 2004 (pp 92-96)
Author(s):TOSHIHIKO KAKU
Department of Cardiovascular Science, Oita University, 1-1 Idaigaoka, Hasama, Oita 8795593, Japan

HIDEAKI OZAKI
Department of Cardiovascular Science, Oita University, 1-1 Idaigaoka, Hasama, Oita 8795593, Japan

SATOSHI ISHII
Department of Biochemistry and Molecular Biology, University of Tokyo, 7-3-1, Bunkyo-ku, Hongo, Tokyo 1130033, Japan

TAKAO SHIMIZU
Department of Biochemistry and Molecular Biology, University of Tokyo, 7-3-1, Bunkyo-ku, Hongo, Tokyo 1130033, Japan

KATSUSHIGE ONO
Department of Cardiovascular Science, Oita University, 1-1 Idaigaoka, Hasama, Oita 8795593, Japan

Abstract:Background Platelet activating factor (PAF) is known as a multifunctional chemical mediator. Recently, it is postulated that PAF could be a source to induce arrhythmias during acute myocardial infarction. However, mechanism of the arrhythmogenetic effects of PAF is still unknown. Methods: Ventricular myocytes were isolated from neonatal rats and wild (WT) / PAF receptor-knock out (PAF-KO) mice. Changes of intracellular calcium concentration in neonatal rat myocytes were measured using Fura-2. L-type calcium channel currents in WT and PAF-KO mice were recorded by voltage clamp method. Results: PAF increased the calcium transient in a dose-dependent manner (10-11-10-6 M), where the effect was diminished by calcium channel antagonist (D600), PAF receptor antagonist (CV-3988), or PKC inhibitor (chelerythline). The increase of L-type calcium channel current by PAF (10-8-107#x002D;6 M) was observed in the WT mice but not in PAF-KO mice. Premature ventricular contractions were provoked by the intravenous injection of PAF (10 ng/g) in wild type mice but not in PAF-KO mice. Conclusion: PAF increases intracellular calcium concentration by activating the L-type calcium channel via PAF receptor-mediated PKC pathways, resulting in various types of premature ventricular contractions.
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