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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Main Authors: O. V. Akopova, L. I. Kolchinskaya, V. I. Nosar, A. N. Smirnov, L. V. Bratus
Format: Article
Language:English
Published: National Academy of Sciences of Ukraine, Palladin Institute of Biochemistry 2020-10-01
Series:The Ukrainian Biochemical Journal
Subjects:
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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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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