Calcium Ions Regulate K+ Uptake into Brain Mitochondria: The Evidence for a Novel Potassium Channel

International Journal of Molecular Sciences

Jolanta Skalska⁴  Piotr Bednarczyk⁴  Marta Piwońska⁴  Bogusz Kulawiak⁴  Grzegorz Wilczynski³  Krzysztof Dołowy¹  Alexei P. Kudin²  Wolfram S. Kunz² 

[1] Department of Biophysics, Agricultural University SGGW, 159 Nowoursynowska St., 02–776 Warsaw, Poland; E-Mail:;Division of Neurochemistry, Department of Epileptology and Life&Brain Center, University Bonn Medical Center, Sigmund-Freud-Str. 25, D-53105 Bonn, Germany; E-Mail:;Laboratory of Molecular and Systemic Neuromorphology, Nencki Institute of Experimental Biology, 3 Pasteur st., 02–093 Warsaw, Poland; E-Mail:;Laboratory of Intracellular Ion Channels, Nencki Institute of Experimental Biology, 3 Pasteur st., 02–093 Warsaw, Poland; E-Mails:

关键词: Mitochondria;    brain;    channel openers;    potassium channel;    iberiotoxin;    NS1619;   

DOI  :  10.3390/ijms10031104

来源: mdpi

【 摘 要 】

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 of mitochondrial respiration. These Ca²⁺ effects can be blocked by iberiotoxin and charybdotoxin, well known inhibitors of large conductance potassium channel (BK_Ca channel). Furthermore, NS1619 – a BK_Ca 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-β₄ subunit (of the BK_Ca channel) antibodies with ~26 kDa proteins of rat brain mitochondria. Immunohistochemical analysis confirmed the predominant occurrence of β₄ subunit in neuronal mitochondria. We hypothesize that the mitochondrial BK_Ca channel represents a calcium sensor, which can contribute to neuronal signal transduction and survival.

【 授权许可】

CC BY   
© 2009 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland. This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).