Brain cell membrane Na+,K(+)-ATPase activity following severe hypoxic injury in the newborn piglet.
This study tests the hypothesis that severe brain hypoxia causes decreased Na+,K(+)-ATPase activity, resulting in permanent alterations in the neuronal cell membranes. Seventeen anesthetized piglets (normoxic control (NC), no recovery after hypoxia (Group 1), 6 h normoxic recovery (Group 2), and 48 h normoxic recovery (Group 3)) were studied. Hypoxia was induced by lowering the FiO2 to maintain PCr/Pi ratio at 25% of baseline for 1 h as monitored by 31P-NMR spectroscopy. PCr/Pi returned to 57% of baseline by 6 h and was normal by 48 h. At termination, cortical tissue Na+,K(+)-ATPase activity was determined. Na+,K(+)-ATPase activity was measured in cortical membrane preparations by determining the rate of ATP hydrolysis. NC membranes had Na+,K(+)-ATPase activity of 58.3 +/- 1.3 microM Pi/mg protein/h (mean +/- S.E.M.). Na+,K(+)-ATPase activity was reduced in Groups 1, 2, and 3 (45.8 +/- 1.3, 47.4 +/- 3.6, 48.7 +/- 2.9 microM Pi/mg protein/h) (P < 0.05 compared to NC). There was no difference in enzyme activity among Groups 1, 2, or 3. The data show that in spite of recovery of neuronal oxidative phosphorylation (PCr/Pi) by 48 h, there is a permanent decrease in Na+,K(+)-ATPase activity in cells that have undergone severe hypoxic injury. The persistent decrease in Na+,K(+)-ATPase activity indicates ongoing cell injury following severe cerebral hypoxia, and that recovery of oxidative phosphorylation as indicated by PCr/Pi values cannot be used as an index of recovery of cell function.
Rosenkrantz
T S
TS
University of Connecticut School of Medicine, Department of Pediatrics, Farmington 06030, USA.
Kubin
J
J
Mishra
O P
OP
Smith
D
D
Delivoria-Papadopoulos
M
M
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D001921:Brain / Q000201:enzymology* / Q000473:pathology; D002462:Cell Membrane / Q000201:enzymology; D000860:Hypoxia / Q000175:diagnosis / Q000201:enzymology* / Q000473:pathology; D009682:Magnetic Resonance Spectroscopy; D010710:Phosphates / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism; D012016:Reference Values; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013552:Swine
D010710:Phosphates; D010725:Phosphocreatine; D000254:Sodium-Potassium-Exchanging ATPase