title: The effect of atp-dependent potassium uptake on mitochondrial functions under acute hypoxia.
abstract: The opening of mitochondrial K(+) АТР-channel (mtK(+) АТР-channel) is supposed to be important in the modulation of mitochondrial functions under hypoxia, but the underlying mechanisms have not been clarified yet. The aim of this work was to study the effect of acute hypoxia on mtK(+) АТР-channel activity and to estimate the contribution of the channel in the modulation of mitochondrial functions. MtK(+) АТР-channel activity was assessed polarographically from the rate of State 4 respiration and by potentiometric monitoring of potassium efflux from deenergized mitochondria. It was shown that hypoxia reliably increased mtK(+) АТР-channel activity, which resulted in the changes of respiration rates (increase of State 4 and suppression of State 3 respiration), uncoupling (the decrease of respiratory control ratio) and suppression of phosphorylation. These effects were well mimicked by mtK(+) АТР-channel opener diazoxide (DZ) in isolated rat liver mitochondria. MtK(+) АТР-channel opening in vitro suppressed phosphorylation too, but increased phosphorylation efficiency, while mtK(+) АТР-channel blockers reduced it dramatically. The correlation was established between mtK(+) АТР-channel activity and the endurance of the rats to physical training under hypoxia. Hypoxia improved physical endurance, but treatment by mtK(+) АТР-channel blockers glibenklamide and 5-hydroxydecanoate (5-HD) prior to hypoxia strongly reduced both the channel activity and the endurance limits. This was in accord with the observation that under glibenklamide and 5-HD administration hypoxia failed to restore mtK(+) АТР-channel activity. Based on the experiments, we came to the conclusion that mtK(+) АТР-channel opening played a decisive role in the regulation of energy metabolism under acute hypoxia via the modulation of phosphorylation system in mitochondria.
authors.affiliation: Circulation Department, Bogomoletz Institute of Physiology, NAS of Ukraine, Bogomoletz str. 4, 01601, Kiev, Ukraine. a-dubensky@mail.ru.
authors.forename: Olga
authors.identifier: http://orcid.org/0000-0002-0928-5087
authors.initials: O
authors.lastname: Akopova
authors.affiliation: Hypoxic States Research Department, Bogomoletz Institute of Physiology, NAS of Ukraine, Kiev, Ukraine.
authors.forename: Valentina
authors.initials: V
authors.lastname: Nosar
authors.affiliation: Hypoxic States Research Department, Bogomoletz Institute of Physiology, NAS of Ukraine, Kiev, Ukraine.
authors.forename: Bronislav
authors.initials: B
authors.lastname: Gavenauskas
authors.affiliation: Hypoxic States Research Department, Bogomoletz Institute of Physiology, NAS of Ukraine, Kiev, Ukraine.
authors.forename: Larissa
authors.initials: L
authors.lastname: Bratus
authors.affiliation: Circulation Department, Bogomoletz Institute of Physiology, NAS of Ukraine, Bogomoletz str. 4, 01601, Kiev, Ukraine.
authors.forename: Liudmila
authors.initials: L
authors.lastname: Kolchinskaya
authors.affiliation: Hypoxic States Research Department, Bogomoletz Institute of Physiology, NAS of Ukraine, Kiev, Ukraine.
authors.forename: Iryna
authors.initials: I
authors.lastname: Mankovska
authors.affiliation: Circulation Department, Bogomoletz Institute of Physiology, NAS of Ukraine, Bogomoletz str. 4, 01601, Kiev, Ukraine.
authors.forename: Vadim
authors.initials: V
authors.lastname: Sagach
mesh_terms: D000208:Acute Disease; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D000860:Hypoxia / Q000378:metabolism* / Q000473:pathology; D017136:Ion Transport; D008297:Male; D008930:Mitochondria, Liver / Q000378:metabolism* / Q000473:pathology; D024101:Mitochondrial Proteins / Q000378:metabolism*; D010101:Oxygen Consumption; D011188:Potassium / Q000378:metabolism*; D051381:Rats; D011921:Rats, Inbred WKY
chemical_list: D024101:Mitochondrial Proteins; D000255:Adenosine Triphosphate; D011188:Potassium
keywords: Acute hypoxia; Phosphorylation; Physical training; State 3 and State 4 respiration; diazoxide; mtK+ АТР-channel