Abstract |
The molecular components of the large-conductance Ca(2+)-activated K(+) channels that are functionally expressed in mitochondria (mitoK(Ca)) in cardiac myocytes have not been identified. Our experimental results show that the transcript corresponding to the large-conductance Ca(2+)-activated K(+) channel beta1-subunit (BK-beta1) is substantially expressed in mammalian heart. A yeast two-hybrid assay showed the BK-beta1 protein can interact with a mitochondrial protein, cytochrome c oxidase subunit I (Cco1). Results from immunocytochemical experiments also demonstrated that BK-beta1 interacted with Cco1 and colocalized in rat cardiac mitochondria. Furthermore, 17beta-estradiol, which enhances the activity of the BK channel alpha-subunit only in the presence of the beta1-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 mitoK(Ca), which had a conductance of approximately 270 pS, was enhanced by 17beta-estradiol and blocked by paxilline. In combination, the present study revealed a new mechanism for the cardioprotective effects of 17beta-estradiol, which include the activation of mitoK(Ca) via the interaction with BK-beta1. BK-beta1 may be an important molecular component that functionally couples with both Cco1 and mitoK(Ca) pore-forming alpha-subunit.
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Authors | Susumu Ohya, Yukiko Kuwata, Kazuho Sakamoto, Katsuhiko Muraki, Yuji Imaizumi |
Journal | American journal of physiology. Heart and circulatory physiology
(Am J Physiol Heart Circ Physiol)
Vol. 289
Issue 4
Pg. H1635-42
(Oct 2005)
ISSN: 0363-6135 [Print] United States |
PMID | 16113069
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Flavoproteins
- Large-Conductance Calcium-Activated Potassium Channel alpha Subunits
- Large-Conductance Calcium-Activated Potassium Channels
- Potassium Channels, Calcium-Activated
- Estradiol
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Topics |
- Amino Acid Sequence
- Animals
- Estradiol
(pharmacology)
- Flavoproteins
(metabolism)
- Humans
- In Vitro Techniques
- Large-Conductance Calcium-Activated Potassium Channel alpha Subunits
- Large-Conductance Calcium-Activated Potassium Channels
- Male
- Mammals
- Mice
- Microscopy, Fluorescence
- Mitochondria
(drug effects, physiology)
- Molecular Sequence Data
- Myocardial Ischemia
(physiopathology)
- Myocytes, Cardiac
(drug effects, physiology)
- Potassium Channels, Calcium-Activated
(genetics, physiology)
- Rats
- Rats, Wistar
- Two-Hybrid System Techniques
- Yeasts
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