Hypoxic Stress Induces Transient Receptor Potential Melastatin 2 (TRPM2) Channel Expression in Adult Rat Cardiac Fibroblasts

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概要

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• When cardiac tissue is exposed to hypoxia, myocytes are damaged, while fibroblasts are activated. However, it is unknown what changes are induced by hypoxia in cardiac fibroblasts. In this study, using the whole cell patch-clamp technique, we investigated the effect of hypoxia on membrane currents in fibroblasts primarily cultured from adult rat hearts. Cardiac fibroblasts were incubated for 24 h under normoxic or hypoxic conditions using Anaeropack. Hypoxia increased a current which reversed at around −20 mV in the cardiac fibroblasts. This current was inhibited by clotrimazole, which is an inhibitor of transient receptor potential melastatin 2 (TRPM2) channel and intermediate-conductance Ca<SUP>2+</SUP>-activated K<SUP>+</SUP> channel (KCa3.1). ADP ribose in the pipette solution enhanced this current. Quantitative RT-PCR revealed that mRNA of TRPM2, but not that of KCa3.1, was increased by hypoxia. RNA interference of TRPM2 prevented the development of the hypoxia-induced current. H<SUB>2</SUB>O<SUB>2</SUB>, an activator of TRPM2 channel, induced a higher [Ca<SUP>2+</SUP>]<SUB>i</SUB> elevation in hypoxia-exposed cardiac fibroblasts than that in normoxia-exposed cells. We conclude that hypoxia induces TRPM2 channel expression in adult rat cardiac fibroblasts.

• 2012-02-20

著者

• Kimura Junko

  Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Toho University

• Kimura J

  Department Of Pharmacology Fukushima Medical University School Of Medicine

• TAKAHASHI Kenji

  Japan Pharmaceutical Manufacturers Association

• Sakamoto Kazuho

  Department Of Molecular And Cellular Pharmacology Graduate School Of Pharmaceutical Sciences Nagoya

• Sakamoto Kazuho

  Department Of Pharmacology School Of Medicine Fukushima Medical University

• Takahashi Kenji

  Department Of Pharmacology

• Takahashi Kenji

  Department Of Atomic Science And Nuclear Engineering Faculty Of Engineering Hokkaido University

• Takahashi Kenji

  Department Of Applied Biological Chemistry Graduate School Of Agriculture Kinki University

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