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Regulation of ROS production by a mitochondrial Ca2+-regulated large-conductance potassium channel

Bogusz Kulawiak 1,  Wolfram Kunz 2,  Adam M. Szewczyk 1

1. Instytut Biologii Doświadczalnej PAN (IBD), Pasteura 3, Warszawa 02-093, Poland
2. Univ.Bonn, Bonn, Germany

Abstract
Potassium channels are present in the inner-mitochondrial membrane. Recently, a large-conductance Ca2+-activated potassium (BKCa) channel was described in heart, glioma and brain mitochondria. Potassium channels play a pivotal role in cytoprotection. Activation of mitoKATP channel with pharmacological agents can lead to cardioprotection and neuroprotection. Similarly, activation of mitochondrial BKCa channel by potassium channel opener NS1619 can lead to cardioprotection. Probably, important role in cytoprotective effects of potassium channel activation can play reactive oxygen species (ROS) produced by mitochondrial respiratory chain. Despite of recent several studies the influence of potassium channels activity on ROS production is not fully recognized.

The activity of BKCa channels is modulated by pharmacological substances such as potassium channel openers; benzimidazolone derivative NS1619 and indol derivatives CGS7181 and CGS7184. The channel is blocked by charybdotoxin, iberiotoxin and paxilline.

The aim of our experiments was to test the influence of mitochondrial BKCa channel activity on mitochondrial ROS production. To do that we isolated rat brain mitochondria and use fluorescence dye phydroxyphenylacetic acid (pHPAA). We used 10mM succinate or 10mM glutamate/succinate as substrates for mitochondrial respiration.

We have found that addition of 1-5μM CGS7184, in potassium medium, decreased ROS production up to 80-85% of control value. NS1619 almost completely inhibited ROS production in dose dependent manner (0.5-8μM). In sodium medium, CGS7184 did not influence ROS production. Similarly, we have observed less inhibition of ROS production by NS1619 in sodium containing medium. What is more, addition of 50nM iberiotoxin, in potassium medium, almost completely inhibited effects of CGS7184.

We conclude that activation of the mitochondrial BKCa channel leads to decrease of ROS production by brain mitochondria.

This study was supported by the Ministry of Science and INformation Society Technologies grant No PBZ-MIN-001/P05/11.

 

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Presentation: Wykład at Zjazd Polskiego Towarzystwa Biochemicznego, Sympozjum H, by Bogusz Kulawiak
See On-line Journal of Zjazd Polskiego Towarzystwa Biochemicznego

Submitted: 2007-04-30 08:14
Revised:   2009-06-07 00:44