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Calcium Ions Regulate K+ Uptake into Brain Mitochondria: The Evidence for a Novel Potassium Channel
Laboratory of Intracellular Ion Channels, Nencki Institute of Experimental Biology, 3 Pasteur st., 02-093 Warsaw, Poland
Department of Biophysics, Agricultural University SGGW, 159 Nowoursynowska St., 02-776 Warsaw, Poland
Laboratory of Molecular and Systemic Neuromorphology, Nencki Institute of Experimental Biology, 3 Pasteur st., 02-093 Warsaw, Poland
Division of Neurochemistry, Department of Epileptology and Life&Brain Center, University Bonn Medical Center, Sigmund-Freud-Str. 25, D-53105 Bonn, Germany
These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 18 February 2009; in revised form: 6 March 2009 / Accepted: 10 March 2009 / Published: 12 March 2009
Abstract: The mitochondrial response to changes of cytosolic calcium concentration has a strong impact on neuronal cell metabolism and viability. We observed that Ca2+ additions to isolated rat brain mitochondria induced in potassium ion containing media a mitochondrial membrane potential depolarization and an accompanying increase ofmitochondrial respiration. These Ca2+ effects can be blocked by iberiotoxin and charybdotoxin, well known inhibitors of large conductance potassium channel (BKCa channel). Furthermore, NS1619 – a BKCa channel opener – induced potassium ion–specific effects on brain mitochondria similar to those induced by Ca2+. These findings suggest the presence of a calcium-activated, large conductance potassium channel (sensitive to charybdotoxin and NS1619), which was confirmed by reconstitution of the mitochondrial inner membrane into planar lipid bilayers. The conductance of the reconstituted channel was 265 pS under gradient (50/450 mM KCl) conditions. Its reversal potential was equal to 50 mV, which proved that the examined channel was cation-selective. We also observed immunoreactivity of anti-b4 subunit (of the BKCa channel) antibodies with ~26 kDa proteins of rat brain mitochondria. Immunohistochemical analysis confirmed the predominant occurrence of b4 subunit in neuronal mitochondria. We hypothesize that the mitochondrial BKCa channel represents a calcium sensor, which can contribute to neuronal signal transduction and survival.
Keywords: Mitochondria; brain; channel openers; potassium channel; iberiotoxin; NS1619
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Skalska, J.; Bednarczyk, P.; Piwońska, M.; Kulawiak, B.; Wilczynski, G.; Dołowy, K.; Kunz, W.S.; Kudin, A.P.; Szewczyk, A. Calcium Ions Regulate K+ Uptake into Brain Mitochondria: The Evidence for a Novel Potassium Channel. Int. J. Mol. Sci. 2009, 10, 1104-1120.
Skalska J, Bednarczyk P, Piwońska M, Kulawiak B, Wilczynski G, Dołowy K, Kunz WS, Kudin AP, Szewczyk A. Calcium Ions Regulate K+ Uptake into Brain Mitochondria: The Evidence for a Novel Potassium Channel. International Journal of Molecular Sciences. 2009; 10(3):1104-1120.
Skalska, Jolanta; Bednarczyk, Piotr; Piwońska, Marta; Kulawiak, Bogusz; Wilczynski, Grzegorz; Dołowy, Krzysztof; Kunz, Wolfram S.; Kudin, Alexei P.; Szewczyk, Adam. 2009. "Calcium Ions Regulate K+ Uptake into Brain Mitochondria: The Evidence for a Novel Potassium Channel." Int. J. Mol. Sci. 10, no. 3: 1104-1120.