Mitochondrial Ca2+-activated K+ Channels More Efficiently Reduce Mitochondrial Ca2+ Overload in Rat Ventricular Myocytes.
From: Mitochondrial Signaling Laboratory, Department of Physiology and Biophysics, College of Medicine, Biohealth Products Research Center, Inje University, 633-165 Gaegeum-Dong, Busanjin-Gu, Busan 613-735, Korea.
American journal of physiology. Heart and circulatory physiology
- Publish Date: Jul 2007
- ISSN: 0363-6135
- Volume: 293
- Issue: 1
- Pages: H307-13
- Medium: Print
- Language: English
- Citation (JAMA): Kang Sung Hyun, Park Won Sun, Kim Nari, et al. Mitochondrial Ca2+-activated K+ Channels More Efficiently Reduce Mitochondrial Ca2+ Overload in Rat Ventricular Myocytes.. Am. J. Physiol. Heart Circ. Physiol. Jul 2007;293:H307-13
Abstract
We investigated the role of the mitochondrial ATP-sensitive K(+) (K(ATP)) channel, the mitochondrial big-conductance Ca(2+)-activated K(+) (BK(Ca)) channel, and the mitochondrial permeability transition pore (MPTP) in the ouabain-induced increase of mitochondrial Ca(2+) in native rat ventricular myocytes by loading cells with rhod 2-AM. To overload mitochondrial Ca(2+), we pretreated cells with ouabain before applying mitochondrial K(ATP) or BK(Ca) channel and/or MPTP opener. Ouabain (1 mM) increased the rhod 2-sensitive fluorescence intensity (160 +/- 5.0% of control), which was dramatically decreased to the control level on application of diazoxide and NS-1619 in a dose-dependent manner (half-inhibition concentrations of 78.3 and 7.78 muM for diazoxide and NS-1619, respectively). This effect was reversed by selective inhibition of the mitochondrial K(ATP) channel by 5-hydroxydecanoate, the mitochondrial BK(Ca) channel by paxilline, and the MPTP by cyclosporin A. Although diazoxide did not efficiently reduce mitochondrial Ca(2+) during prolonged exposure to ouabain, NS-1619 reduced mitochondrial Ca(2+). These results suggest that although mitochondrial BK(Ca) and K(ATP) channels contribute to reduction of ouabain-induced mitochondrial Ca(2+) overload, activation of the mitochondrial BK(Ca) channel more efficiently reduces ouabain-induced mitochondrial Ca(2+) overload in our experimental model.
Mesh Headings (Keywords): Animals, Calcium, Cells, Cultured, Heart Ventricles, Ion Channel Gating, Mitochondria, Mitochondrial Proteins, Myocytes, Cardiac, Potassium Channels, Calcium-Activated, Rats, Rats, Sprague-Dawley
Check for Full Text / PubMed Unique Identifier (PMID): 17351070
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