Coupling among energy failure, loss of ion homeostasis, and phospholipase A2 and C activation during ischemia.
The objective of the present experiments was to correlate changes in cellular energy metabolism, dissipative ion fluxes, and lipolysis during the first 90 s of ischemia and, hence, to establish whether phospholipase A2 or phospholipase C is responsible for the early accumulation of phospholipid hydrolysis products. Ischemia was induced for 15-90 s in rats, extracellular K+ (K+e) was recorded, and neocortex was frozen in situ for measurements of labile tissue metabolites, free fatty acids, and diacylglycerides. Ischemia of 15- and 30-s duration gave rise to a decrease in phosphocreatine concentration and a decline in the ATP/free ADP ratio. Although these changes were accompanied by an activation of K+ conductances, there were no changes in free fatty acids until after 60 s, when free arachidonic acid accumulated. An increase in other free fatty acids and in total diacylglceride content did not occur until after anoxic depolarization. The results demonstrate that the early functional changes, such as activation of K+ conductances, are unrelated to changes in lipids or lipid mediators. They furthermore suggest that the initial lipolysis occurs via both phospholipase A2 and phospholipase C, which are activated when membrane depolarization leads to influx of calcium into cells.
Katsura
K
K
Laboratory for Experimental Brain Research, Experimental Research Center, University of Lund, Sweden.
Rodriguez de Turco
E B
EB
Folbergrová
J
J
Bazan
N G
NG
Siesjö
B K
BK
D000227:Adenine Nucleotides / Q000378:metabolism*; D000818:Animals; D001794:Blood Pressure; D002245:Carbon Dioxide / Q000097:blood; D002540:Cerebral Cortex / Q000378:metabolism; D003404:Creatinine / Q000378:metabolism; D004075:Diglycerides / Q000737:chemistry / Q000378:metabolism; D004734:Energy Metabolism; D004789:Enzyme Activation; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D006706:Homeostasis; D002546:Ischemic Attack, Transient / Q000201:enzymology / Q000378:metabolism* / Q000503:physiopathology; D007700:Kinetics; D008297:Male; D010100:Oxygen / Q000097:blood; D010313:Partial Pressure; D010725:Phosphocreatine / Q000378:metabolism; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D011188:Potassium / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D010738:Type C Phospholipases / Q000378:metabolism*
D000227:Adenine Nucleotides; D004075:Diglycerides; D005230:Fatty Acids, Nonesterified; D010725:Phosphocreatine; D002245:Carbon Dioxide; D003404:Creatinine; D010741:Phospholipases A; D054467:Phospholipases A2; D010738:Type C Phospholipases; D011188:Potassium; D010100:Oxygen