Oxygen-induced Regulation of Na/K ATPase in cerebellar granule cells.
Adjustment of the Na/K ATPase activity to changes in oxygen availability is a matter of survival for neuronal cells. We have used freshly isolated rat cerebellar granule cells to study oxygen sensitivity of the Na/K ATPase function. Along with transport and hydrolytic activity of the enzyme we have monitored alterations in free radical production, cellular reduced glutathione, and ATP levels. Both active K(+) influx and ouabain-sensitive inorganic phosphate production were maximal within the physiological pO(2) range of 3-5 kPa. Transport and hydrolytic activity of the Na/K ATPase was equally suppressed under hypoxic and hyperoxic conditions. The ATPase response to changes in oxygenation was isoform specific and limited to the alpha1-containing isozyme whereas alpha2/3-containing isozymes were oxygen insensitive. Rapid activation of the enzyme within a narrow window of oxygen concentrations did not correlate with alterations in the cellular ATP content or substantial shifts in redox potential but was completely abolished when NO production by the cells was blocked by l-NAME. Taken together our observations suggest that NO and its derivatives are involved in maintenance of high Na/K ATPase activity under physiological conditions.
Petrushanko
Irina Yu
IY
Institute of Veterinary Physiology, Vetsuisse Faculty and Zurich Centre of Integrative Human Physiology, University of Zurich, Zurich CH-8057, Switzerland.
Bogdanov
Nikolai B
NB
Lapina
N
N
Boldyrev
Alexander A
AA
Gassmann
Max
M
Bogdanova
Anna Yu
AY
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D015687:Cell Hypoxia / Q000502:physiology; D002531:Cerebellum / Q000201:enzymology*; D004789:Enzyme Activation; D005978:Glutathione / Q000378:metabolism; D006868:Hydrolysis; D007527:Isoenzymes / Q000502:physiology; D008297:Male; D009474:Neurons / Q000201:enzymology*; D009589:Nitrogen Oxides / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D010313:Partial Pressure; D011188:Potassium / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D007527:Isoenzymes; D009589:Nitrogen Oxides; D017382:Reactive Oxygen Species; D000255:Adenosine Triphosphate; D000254:Sodium-Potassium-Exchanging ATPase; D005978:Glutathione; D011188:Potassium; D010100:Oxygen