Cardioprotective effects of estradiol include the activation of large-conductance Ca2+-activated K+ channels in cardiac mitochondria
Susumu Ohya, Yukiko Kuwata, Kazuho Sakamoto, Katsuhiko Muraki, and Yuji Imaizumi
Department of Molecular and Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan
Submitted 7 January 2005 ; accepted in final form 27 May 2005
The molecular components of the large-conductance Ca2+-activated K+ channels that are functionally expressed in mitochondria (mitoKCa) in cardiac myocytes have not been identified. Our experimental results show that the transcript corresponding to the large-conductance Ca2+-activated K+ channel 1-subunit (BK-1) is substantially expressed in mammalian heart. A yeast two-hybrid assay showed the BK-1 protein can interact with a mitochondrial protein, cytochrome c oxidase subunit I (Cco1). Results from immunocytochemical experiments also demonstrated that BK-1 interacted with Cco1 and colocalized in rat cardiac mitochondria. Furthermore, 17-estradiol, which enhances the activity of the BK channel -subunit only in the presence of the 1-subunit, significantly increased flavoprotein oxidation in rat ventricle myocytes and decreased the rate of cell death under simulated ischemia. Single-channel recordings from mitochondrial inner membrane indicated that the activity of mitoKCa, which had a conductance of 270 pS, was enhanced by 17-estradiol and blocked by paxilline. In combination, the present study revealed a new mechanism for the cardioprotective effects of 17-estradiol, which include the activation of mitoKCa via the interaction with BK-1. BK-1 may be an important molecular component that functionally couples with both Cco1 and mitoKCa pore-forming -subunit.
これは虚血再灌流障害を考えるに当たって，非常に重要な論文です。
ミトコンドリアのBKcaはPKA dependentにミトコンドリア内膜を過分極させ，ミトコンドリアへのCalcium流入を抑制することが，千葉大の佐藤先生たちにより，Circulationに報告されています。
Susumu Ohya, Yukiko Kuwata, Kazuho Sakamoto, Katsuhiko Muraki, and Yuji Imaizumi
Department of Molecular and Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan
Submitted 7 January 2005 ; accepted in final form 27 May 2005
The molecular components of the large-conductance Ca2+-activated K+ channels that are functionally expressed in mitochondria (mitoKCa) in cardiac myocytes have not been identified. Our experimental results show that the transcript corresponding to the large-conductance Ca2+-activated K+ channel 1-subunit (BK-1) is substantially expressed in mammalian heart. A yeast two-hybrid assay showed the BK-1 protein can interact with a mitochondrial protein, cytochrome c oxidase subunit I (Cco1). Results from immunocytochemical experiments also demonstrated that BK-1 interacted with Cco1 and colocalized in rat cardiac mitochondria. Furthermore, 17-estradiol, which enhances the activity of the BK channel -subunit only in the presence of the 1-subunit, significantly increased flavoprotein oxidation in rat ventricle myocytes and decreased the rate of cell death under simulated ischemia. Single-channel recordings from mitochondrial inner membrane indicated that the activity of mitoKCa, which had a conductance of 270 pS, was enhanced by 17-estradiol and blocked by paxilline. In combination, the present study revealed a new mechanism for the cardioprotective effects of 17-estradiol, which include the activation of mitoKCa via the interaction with BK-1. BK-1 may be an important molecular component that functionally couples with both Cco1 and mitoKCa pore-forming -subunit.
これは虚血再灌流障害を考えるに当たって，非常に重要な論文です。
ミトコンドリアのBKcaはPKA dependentにミトコンドリア内膜を過分極させ，ミトコンドリアへのCalcium流入を抑制することが，千葉大の佐藤先生たちにより，Circulationに報告されています。
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