ATP-sensitive potassium transport in rat brain mitochondria is highly sensitive to mK(ATP) channels openers: a light scattering study
The aspects of ATP-sensitive K+ transport regulation by mitochondrial K+,ATP-sensitive (mKATP) channels openers are important for understanding the properties of these channels. The effect of KATP channels openers (KCOs) diazoxide and pinacidil on ATP-sensitive K+ transport in isolated brain mitocho...
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National Academy of Sciences of Ukraine, Palladin Institute of Biochemistry
2020-10-01
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Series: | The Ukrainian Biochemical Journal |
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Online Access: | http://ukrbiochemjournal.org/wp-content/uploads/2020/11/Akopova_5_20.pdf |
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author | O. V. Akopova L. I. Kolchinskaya V. I. Nosar A. N. Smirnov L. V. Bratus |
author_facet | O. V. Akopova L. I. Kolchinskaya V. I. Nosar A. N. Smirnov L. V. Bratus |
author_sort | O. V. Akopova |
collection | DOAJ |
description | The aspects of ATP-sensitive K+ transport regulation by mitochondrial K+,ATP-sensitive (mKATP) channels openers are important for understanding the properties of these channels. The effect of KATP channels openers (KCOs) diazoxide and pinacidil on ATP-sensitive K+ transport in isolated brain mitochondria was studied in the absence and the presence of MgATP using light scattering technique. Without MgATP we observed high sensitivity of ATP-sensitive K+ transport to both drugs with full activation at ≤ 0.5 µM. ATP-sensitive K+ transport was specifically blocked by ATP in the presence of Mg2+. Neither Mg2+ nor ATP affected Vmax of ATP-sensitive K+ transport activated by KCOs, but MgATP shifted the activation curve to micromolar scale. The blockage of ATP-sensitive K+ transport by KATP channels blockers glibenclamide and 5-hydroxydecanoate in the absence and the presence of MgATP proved the sensitivity of ATP-sensitive K+ transport to the blockers of mKATP channel. Full activation of mKATP channel by diazoxide and pinacidil on sub-micromolar scale in the absence of MgATP was shown. The sensitivity of ATP-sensitive K+ transport to the known modulators of mKATP channel (diazoxide, pinacidil, glibenclamide, 5-HD and MgATP) proved the identity of ATP-sensitive K+ transport with mKATP channel activity. Based on our studies, we hypothesized that mKATP channel might comprise high affinity sites for KCOs binding screened by MgATP. The results of this work reveal novel not described earlier aspects of the regulation of ATP-sensitive K+ transport by mKATP channels openers, important for understanding of mKATP channel properties. |
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issn | 2409-4943 2413-5003 |
language | English |
last_indexed | 2024-03-09T07:30:10Z |
publishDate | 2020-10-01 |
publisher | National Academy of Sciences of Ukraine, Palladin Institute of Biochemistry |
record_format | Article |
series | The Ukrainian Biochemical Journal |
spelling | doaj.art-57e6dd42a26c44098fe0f54945d288202023-12-03T06:26:36ZengNational Academy of Sciences of Ukraine, Palladin Institute of BiochemistryThe Ukrainian Biochemical Journal2409-49432413-50032020-10-0192551410.15407/ubj92.05.005ATP-sensitive potassium transport in rat brain mitochondria is highly sensitive to mK(ATP) channels openers: a light scattering studyO. V. Akopova0https://orcid.org/0000-0002-0928-5087L. I. Kolchinskaya1V. I. Nosar2A. N. Smirnov3L. V. Bratus4Bogomoletz Institute of Physiology, National Academy of Sciences of Ukraine, KyivBogomoletz Institute of Physiology, National Academy of Sciences of Ukraine, KyivBogomoletz Institute of Physiology, National Academy of Sciences of Ukraine, KyivBogomoletz Institute of Physiology, National Academy of Sciences of Ukraine, KyivBogomoletz Institute of Physiology, National Academy of Sciences of Ukraine, KyivThe aspects of ATP-sensitive K+ transport regulation by mitochondrial K+,ATP-sensitive (mKATP) channels openers are important for understanding the properties of these channels. The effect of KATP channels openers (KCOs) diazoxide and pinacidil on ATP-sensitive K+ transport in isolated brain mitochondria was studied in the absence and the presence of MgATP using light scattering technique. Without MgATP we observed high sensitivity of ATP-sensitive K+ transport to both drugs with full activation at ≤ 0.5 µM. ATP-sensitive K+ transport was specifically blocked by ATP in the presence of Mg2+. Neither Mg2+ nor ATP affected Vmax of ATP-sensitive K+ transport activated by KCOs, but MgATP shifted the activation curve to micromolar scale. The blockage of ATP-sensitive K+ transport by KATP channels blockers glibenclamide and 5-hydroxydecanoate in the absence and the presence of MgATP proved the sensitivity of ATP-sensitive K+ transport to the blockers of mKATP channel. Full activation of mKATP channel by diazoxide and pinacidil on sub-micromolar scale in the absence of MgATP was shown. The sensitivity of ATP-sensitive K+ transport to the known modulators of mKATP channel (diazoxide, pinacidil, glibenclamide, 5-HD and MgATP) proved the identity of ATP-sensitive K+ transport with mKATP channel activity. Based on our studies, we hypothesized that mKATP channel might comprise high affinity sites for KCOs binding screened by MgATP. The results of this work reveal novel not described earlier aspects of the regulation of ATP-sensitive K+ transport by mKATP channels openers, important for understanding of mKATP channel properties.http://ukrbiochemjournal.org/wp-content/uploads/2020/11/Akopova_5_20.pdfmitochondrial k(atp) channelbrainpotassium transportdiazoxidepinacidil |
spellingShingle | O. V. Akopova L. I. Kolchinskaya V. I. Nosar A. N. Smirnov L. V. Bratus ATP-sensitive potassium transport in rat brain mitochondria is highly sensitive to mK(ATP) channels openers: a light scattering study The Ukrainian Biochemical Journal mitochondrial k(atp) channel brain potassium transport diazoxide pinacidil |
title | ATP-sensitive potassium transport in rat brain mitochondria is highly sensitive to mK(ATP) channels openers: a light scattering study |
title_full | ATP-sensitive potassium transport in rat brain mitochondria is highly sensitive to mK(ATP) channels openers: a light scattering study |
title_fullStr | ATP-sensitive potassium transport in rat brain mitochondria is highly sensitive to mK(ATP) channels openers: a light scattering study |
title_full_unstemmed | ATP-sensitive potassium transport in rat brain mitochondria is highly sensitive to mK(ATP) channels openers: a light scattering study |
title_short | ATP-sensitive potassium transport in rat brain mitochondria is highly sensitive to mK(ATP) channels openers: a light scattering study |
title_sort | atp sensitive potassium transport in rat brain mitochondria is highly sensitive to mk atp channels openers a light scattering study |
topic | mitochondrial k(atp) channel brain potassium transport diazoxide pinacidil |
url | http://ukrbiochemjournal.org/wp-content/uploads/2020/11/Akopova_5_20.pdf |
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