BK channel openers inhibit ROS production of isolated rat brain mitochondria
To delineate the potential mechanism of neuroprotective effects of potassium channel openers we have investigated, how Ca 2+-activated large conductance potassium channel (BK Ca channel) openers influence the production of reactive oxygen species (ROS) by rat brain mitochondria, since mitochondrial...
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| Veröffentlicht in: | Experimental neurology 2008-08, Vol.212 (2), p.543-547 |
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| creator | Kulawiak, Bogusz Kudin, Alexei P. Szewczyk, Adam Kunz, Wolfram S. |
| description | To delineate the potential mechanism of neuroprotective effects of potassium channel openers we have investigated, how Ca
2+-activated large conductance potassium channel (BK
Ca channel) openers influence the production of reactive oxygen species (ROS) by rat brain mitochondria, since mitochondrial generation of ROS is known to have a crucial influence on neuronal survival. We studied the effects of BK
Ca channel openers CGS 7184 and NS 1619 on hydrogen peroxide production rate of isolated rat brain mitochondria. In K
+-containing media 3 μM of both channel openers reduced the hydrogen peroxide production rates by approximately 20%. This effect was not observed in Na
+-containing media. This potassium-dependent partial inhibition of hydrogen peroxide production was found to be sensitive to the selective blockers of BK
Ca channel iberiotoxin and charybdotoxin applied in nanomolar concentrations. Taken together, our data are compatible with the viewpoint that the opening of a Ca
2+-activated large conductance potassium channel being localised in the inner membrane of brain mitochondria inhibits ROS production by respiratory chain complex I. This finding is suggested to explain the beneficial effects of BK potassium channel openers on neuronal survival. |
| doi_str_mv | 10.1016/j.expneurol.2008.05.004 |
| format | Article |
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2+-activated large conductance potassium channel (BK
Ca channel) openers influence the production of reactive oxygen species (ROS) by rat brain mitochondria, since mitochondrial generation of ROS is known to have a crucial influence on neuronal survival. We studied the effects of BK
Ca channel openers CGS 7184 and NS 1619 on hydrogen peroxide production rate of isolated rat brain mitochondria. In K
+-containing media 3 μM of both channel openers reduced the hydrogen peroxide production rates by approximately 20%. This effect was not observed in Na
+-containing media. This potassium-dependent partial inhibition of hydrogen peroxide production was found to be sensitive to the selective blockers of BK
Ca channel iberiotoxin and charybdotoxin applied in nanomolar concentrations. Taken together, our data are compatible with the viewpoint that the opening of a Ca
2+-activated large conductance potassium channel being localised in the inner membrane of brain mitochondria inhibits ROS production by respiratory chain complex I. This finding is suggested to explain the beneficial effects of BK potassium channel openers on neuronal survival.</description><identifier>ISSN: 0014-4886</identifier><identifier>EISSN: 1090-2430</identifier><identifier>DOI: 10.1016/j.expneurol.2008.05.004</identifier><identifier>PMID: 18572168</identifier><identifier>CODEN: EXNEAC</identifier><language>eng</language><publisher>Amsterdam: Elsevier Inc</publisher><subject>Animals ; Benzimidazoles - pharmacology ; Biological and medical sciences ; BK channel opener ; Brain - ultrastructure ; Brain mitochondria ; Dose-Response Relationship, Drug ; Esters - pharmacology ; Hydrogen Peroxide - pharmacology ; Indoles - pharmacology ; Ion Channel Gating - drug effects ; Ion Channel Gating - physiology ; Large-Conductance Calcium-Activated Potassium Channels - physiology ; Medical sciences ; Membrane Potential, Mitochondrial - drug effects ; Membrane Potential, Mitochondrial - physiology ; Membrane Potential, Mitochondrial - radiation effects ; Mitochondria - drug effects ; Mitochondria - metabolism ; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis ; Neurology ; Potassium Channel Blockers - pharmacology ; Rats ; Rats, Wistar ; Reactive Oxygen Species - metabolism ; ROS production</subject><ispartof>Experimental neurology, 2008-08, Vol.212 (2), p.543-547</ispartof><rights>2008 Elsevier Inc.</rights><rights>2008 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c430t-47426afee71840aa89a27d27c26d4f9e05f2c8d5d611c8d7a9c955ba57d45c833</citedby><cites>FETCH-LOGICAL-c430t-47426afee71840aa89a27d27c26d4f9e05f2c8d5d611c8d7a9c955ba57d45c833</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.expneurol.2008.05.004$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>315,782,786,3554,27933,27934,46004</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=20563174$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18572168$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kulawiak, Bogusz</creatorcontrib><creatorcontrib>Kudin, Alexei P.</creatorcontrib><creatorcontrib>Szewczyk, Adam</creatorcontrib><creatorcontrib>Kunz, Wolfram S.</creatorcontrib><title>BK channel openers inhibit ROS production of isolated rat brain mitochondria</title><title>Experimental neurology</title><addtitle>Exp Neurol</addtitle><description>To delineate the potential mechanism of neuroprotective effects of potassium channel openers we have investigated, how Ca
2+-activated large conductance potassium channel (BK
Ca channel) openers influence the production of reactive oxygen species (ROS) by rat brain mitochondria, since mitochondrial generation of ROS is known to have a crucial influence on neuronal survival. We studied the effects of BK
Ca channel openers CGS 7184 and NS 1619 on hydrogen peroxide production rate of isolated rat brain mitochondria. In K
+-containing media 3 μM of both channel openers reduced the hydrogen peroxide production rates by approximately 20%. This effect was not observed in Na
+-containing media. This potassium-dependent partial inhibition of hydrogen peroxide production was found to be sensitive to the selective blockers of BK
Ca channel iberiotoxin and charybdotoxin applied in nanomolar concentrations. Taken together, our data are compatible with the viewpoint that the opening of a Ca
2+-activated large conductance potassium channel being localised in the inner membrane of brain mitochondria inhibits ROS production by respiratory chain complex I. This finding is suggested to explain the beneficial effects of BK potassium channel openers on neuronal survival.</description><subject>Animals</subject><subject>Benzimidazoles - pharmacology</subject><subject>Biological and medical sciences</subject><subject>BK channel opener</subject><subject>Brain - ultrastructure</subject><subject>Brain mitochondria</subject><subject>Dose-Response Relationship, Drug</subject><subject>Esters - pharmacology</subject><subject>Hydrogen Peroxide - pharmacology</subject><subject>Indoles - pharmacology</subject><subject>Ion Channel Gating - drug effects</subject><subject>Ion Channel Gating - physiology</subject><subject>Large-Conductance Calcium-Activated Potassium Channels - physiology</subject><subject>Medical sciences</subject><subject>Membrane Potential, Mitochondrial - drug effects</subject><subject>Membrane Potential, Mitochondrial - physiology</subject><subject>Membrane Potential, Mitochondrial - radiation effects</subject><subject>Mitochondria - drug effects</subject><subject>Mitochondria - metabolism</subject><subject>Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis</subject><subject>Neurology</subject><subject>Potassium Channel Blockers - pharmacology</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>ROS production</subject><issn>0014-4886</issn><issn>1090-2430</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE1P3DAURa2qVZlS_gJ4U3YJz44dO0uK6IcYCQnK2vLYLxqPMvbUThD8-2Y0I7pkdTfn3Xd1CLlgUDNg7dWmxpddxCmnoeYAugZZA4gPZMGgg4qLBj6SBQATldC6PSFfStkAQCe4-kxOmJaKs1YvyPL7HXVrGyMONO0wYi40xHVYhZE-3D_SXU5-cmNIkaaehpIGO6Kn2Y50lW2IdBvG5NYp-hzsV_Kpt0PBs2Oekqcft39uflXL-5-_b66XlZt3jZVQgre2R1RMC7BWd5Yrz5XjrRd9hyB77rSXvmVsTmU710m5slJ5IZ1umlNyeeid1_2dsIxmG4rDYbAR01RM2zVCK63fBVnXNKyR-0Z1AF1OpWTszS6Hrc2vhoHZGzcb82bc7I0bkGY2Pl-eH19Mqy36_3dHxTPw7QjY4uzQZxtdKG8cB9k2TO2Lrg8czuaeA2ZTXMDo0IeMbjQ-hXfH_AP3nqNc</recordid><startdate>20080801</startdate><enddate>20080801</enddate><creator>Kulawiak, Bogusz</creator><creator>Kudin, Alexei P.</creator><creator>Szewczyk, Adam</creator><creator>Kunz, Wolfram S.</creator><general>Elsevier Inc</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7TK</scope><scope>7X8</scope></search><sort><creationdate>20080801</creationdate><title>BK channel openers inhibit ROS production of isolated rat brain mitochondria</title><author>Kulawiak, Bogusz ; Kudin, Alexei P. ; Szewczyk, Adam ; Kunz, Wolfram S.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c430t-47426afee71840aa89a27d27c26d4f9e05f2c8d5d611c8d7a9c955ba57d45c833</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Animals</topic><topic>Benzimidazoles - pharmacology</topic><topic>Biological and medical sciences</topic><topic>BK channel opener</topic><topic>Brain - ultrastructure</topic><topic>Brain mitochondria</topic><topic>Dose-Response Relationship, Drug</topic><topic>Esters - pharmacology</topic><topic>Hydrogen Peroxide - pharmacology</topic><topic>Indoles - pharmacology</topic><topic>Ion Channel Gating - drug effects</topic><topic>Ion Channel Gating - physiology</topic><topic>Large-Conductance Calcium-Activated Potassium Channels - physiology</topic><topic>Medical sciences</topic><topic>Membrane Potential, Mitochondrial - drug effects</topic><topic>Membrane Potential, Mitochondrial - physiology</topic><topic>Membrane Potential, Mitochondrial - radiation effects</topic><topic>Mitochondria - drug effects</topic><topic>Mitochondria - metabolism</topic><topic>Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis</topic><topic>Neurology</topic><topic>Potassium Channel Blockers - pharmacology</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Reactive Oxygen Species - metabolism</topic><topic>ROS production</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kulawiak, Bogusz</creatorcontrib><creatorcontrib>Kudin, Alexei P.</creatorcontrib><creatorcontrib>Szewczyk, Adam</creatorcontrib><creatorcontrib>Kunz, Wolfram S.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Experimental neurology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kulawiak, Bogusz</au><au>Kudin, Alexei P.</au><au>Szewczyk, Adam</au><au>Kunz, Wolfram S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>BK channel openers inhibit ROS production of isolated rat brain mitochondria</atitle><jtitle>Experimental neurology</jtitle><addtitle>Exp Neurol</addtitle><date>2008-08-01</date><risdate>2008</risdate><volume>212</volume><issue>2</issue><spage>543</spage><epage>547</epage><pages>543-547</pages><issn>0014-4886</issn><eissn>1090-2430</eissn><coden>EXNEAC</coden><abstract>To delineate the potential mechanism of neuroprotective effects of potassium channel openers we have investigated, how Ca
2+-activated large conductance potassium channel (BK
Ca channel) openers influence the production of reactive oxygen species (ROS) by rat brain mitochondria, since mitochondrial generation of ROS is known to have a crucial influence on neuronal survival. We studied the effects of BK
Ca channel openers CGS 7184 and NS 1619 on hydrogen peroxide production rate of isolated rat brain mitochondria. In K
+-containing media 3 μM of both channel openers reduced the hydrogen peroxide production rates by approximately 20%. This effect was not observed in Na
+-containing media. This potassium-dependent partial inhibition of hydrogen peroxide production was found to be sensitive to the selective blockers of BK
Ca channel iberiotoxin and charybdotoxin applied in nanomolar concentrations. Taken together, our data are compatible with the viewpoint that the opening of a Ca
2+-activated large conductance potassium channel being localised in the inner membrane of brain mitochondria inhibits ROS production by respiratory chain complex I. This finding is suggested to explain the beneficial effects of BK potassium channel openers on neuronal survival.</abstract><cop>Amsterdam</cop><pub>Elsevier Inc</pub><pmid>18572168</pmid><doi>10.1016/j.expneurol.2008.05.004</doi><tpages>5</tpages></addata></record> |
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| subjects | Animals Benzimidazoles - pharmacology Biological and medical sciences BK channel opener Brain - ultrastructure Brain mitochondria Dose-Response Relationship, Drug Esters - pharmacology Hydrogen Peroxide - pharmacology Indoles - pharmacology Ion Channel Gating - drug effects Ion Channel Gating - physiology Large-Conductance Calcium-Activated Potassium Channels - physiology Medical sciences Membrane Potential, Mitochondrial - drug effects Membrane Potential, Mitochondrial - physiology Membrane Potential, Mitochondrial - radiation effects Mitochondria - drug effects Mitochondria - metabolism Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis Neurology Potassium Channel Blockers - pharmacology Rats Rats, Wistar Reactive Oxygen Species - metabolism ROS production |
| title | BK channel openers inhibit ROS production of isolated rat brain mitochondria |
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