To examine the relationships between brain glycolysis, ion transport, and mitochondrial reduction/oxidation (redox) activity, extracellular potassium ion activity (K+0) and redox shifts of cytochrome oxidase (cytochrome a,a3) were recorded previous to and during superfusion of rat cerebral cortex with the glycolytic inhibitor iodoacetic acid (IAA). IAA produced oxidation of cytochrome a,a3, increased local oxygenation, increased K+0, and, in response to neuronal activation, slowed rates of K+0 reaccumulation. Rates of rereduction of cytochrome a,a3, after the oxidation of this cytochrome by stimulation, were also slowed by IAA. These effects of IAA demonstrate the dependence of K+0 reaccumulation on the integrity of glycolysis, support the concept that active processes are involved in brain ion transport, and suggest a link between ATP supplied by glycolysis and ion transport activity. These data are also compatible with the suggestion that residual dysfunctions after brain ischemia result from derangements in glycolytic functioning rather than from limitations in oxygen availability or oxidative metabolic activity.
AgardhC-DFolbergrovaJSiesjoBK, (1978) Cerebra metabolic changes in profound, insulin-induced hypoglycemia, and the recovery period following glucose administration. J Neurochem31:1135–1142
2.
AstrupJNorbergK, (1976) Potassium activity in cerebral cortex in rats during progressive severe hypoglycemia. Brain Res103:418–423
3.
AstrupJBlennowGNilssonB, (1979) Effects of reduced cerebral blood flow upon EEG pattern, cerebral extracellular potassium and energy metabolism in the rat cortex during bicuculline-induced seizures. Brain Res177:115–126
4.
AstrupJSorensenPMSorensenHR, (1981) Oxygen and glucose consumption related to Na+-K+ transport in canine brain. Stroke12:726–730
5.
BryanRMJobsisFF, (1983) The cerebral redox state in cats during severe insulin induced hypoglycemia. Brain Res279:266–270
6.
BryanRMJobsisFF, (1986) Insufficient supply of reducing equivalents to the respiratory chain in cerebral cortex during severe insulin-induced hypoglycemia in cats. J Cereb Blood Flow Metab6:296–291
7.
ChanceBWilliamsGR, (1956) The respiratory chain and oxidative phosphorylation. Adv Enzymol17:65–134
CoxDWGBachelardHS, (1982) Attenuation of evoked field potentials from dentate granule cells by low glucose, pyrvate + malate, and sodium fluoride. Brain Res239:527–534
10.
DirksBHankeJKrieglesteinJStockRWickopG, (1980) Studies on the linkage of energy metabolism and neuronal activity in the isolated perfused rat brain. J Neurochem35:311–317
11.
DuckrowRBLaMannaJCRosenthalM, (1981) Disparate recovery of resting and stimulated oxidative metabolism following transient ischemia. Stroke12:677–686
12.
DuckrowRBLaMannaJCRosenthalM, (1982) Sensitive and inexpensive dual wavelength reflection spectrophotometry using interference filters. Anal Biochem125:13–23
13.
DuckrowRBSickTJRosenthalM, (1983) Potassium transport dysfunction after cerebral ischemia: Relationships between ion homeostasis and oxidative metabolism. J Cereb Blood Flow Metab3:S347–S348
14.
DuncanDB, (1955) Multiple range and multiple F tests. Biometrics11:1–42
15.
FerrendelliJAChangMM, (1973) Brain metabolism during hypoglycaemia. Effect of insulin on regional CNS glucose and energy reserves in mice. Arch Neurol28:173–177
16.
GhajarJBGPlumFDuffyTE, (1982) Cerebral oxidative metabolism and blood flow during acute hypoglycemia and recovery in unanesthetized rats. J Neurochem38:397–409
17.
HansenAJ, (1985) Effect of anoxia on ion distribution in the brain. Physiol Rev65: 101–148
18.
HeinemannULuxHD, (1975) Undershoots following stimulus-induced rises of extracellular potassium concentration in cerebral cortex of cat. Brain Res93:63–76
19.
JobsisFFKeizerJHLaMannaJCRosenthalM, (1977) In vivo reflectance spectrophotometry of cytochrome a,a3 in the intact cerebral cortex of the cat. J Appl Physiol43:858–872
20.
KreismanNRSickTJBruleyDF, (1979) Local oxygen tension and its relationship to unit activity during penicillin interictal discharges in the bullfrog hippocampus. Electroencephalogr Clin Neurophysiol46:619–633
21.
KrizNSykovaEVyklickyL, (1975) Extracellular potassium changes in the spinal cord of the cat and their relation to slow potentials, active transport and impulse transmission. J Physiol249:167–182
22.
KrolickiLLeniger-FollertE, (1980) Oxygen supply of the brain cortex (rat) during severe hypoglycemia. Pflugers Arch387:121–126
23.
LaMannaJCSickTPikarskySMRosenthalM, (1987) Detection of an oxidizable fraction of cytochrome oxidase in intact rat brain. Am J Physiol253:C477–C483
24.
LewisDVSchuetteWH, (1975) NADH fluorescence and (K+) changes during hippocampal stimulation. J Neurophysiol38:405–417
25.
LewisDVSchuetteWH, (1976) NADH fluorescence, K+o and oxygen consumption in cat cerebral cortex during direct cortical stimulation. Brain Res110:523–535
26.
LewisLDLjunggrenBNorbergKSiesjoBK, (1974a) Changes in carbohydrate substrates, amino acids, and ammonia in the brain during insulin-induced hypoglycaemia. J Neurochern23:659–671
27.
LewisLDLjunggrenBRatchesonRASiesjoBK, (1974b) Cerebral energy state in insulin-induced hypoglycaemia, related to blood glucose and to EEG. J Neurochem23:673–679
28.
LiptonPRobackerK, (1983) Glycolysis and brain function: (K+)o stimulation of protein synthesis and K+ uptake require glycolysis. Fed Proc42:2875–2880
29.
LothmanELaMannaJCCordingleyGRosenthalMSomjenGG, (1975) Responses of electrical potential, potassium levels and oxidative metabolic activity of the cerebral neocortex of cats. Brain Res88:15–36
30.
MayevskyAChanceB, (1975) Metabolic responses of the awake cerebral cortex to anoxia, hypoxia, spreading depression and epileptiform activity. Brain Res98:149–165
31.
MercerRWDunhamPB, (1981) Membrane-bound ATP fuels the Na+/K+ pump. J Gen Physiol78:547–568
32.
MilitoSJRaffinCNRosenthalMSickTJ, (1986) Brain potassium ion homeostasis and mitochondrial redox activity during hypoxia and glycolytic inhibition. Neurosci Abstr12:694
33.
MilitoSJRaffinCNRosenthalMSickTJ, (1988) Potassium ion homeostasis and mitochondrial redox activity in brain: Relative changes as indicators of hypoxia. J Cereb Blood Flow Metab8:155–162
34.
PaulRJ, (1983) Functional compartmentalization of oxidative and glycolytic metabolism in vascular smooth muscle. Am J Physiol244:C399–C409
35.
PaulRJBauerMPeaseW, (1979) Vascular smooth muscle; aerobic glycolysis linked to sodium and potassium transport processes. Science206:1414–1416
36.
ProverbioFHoffmanJF, (1977) Membrane compartmentalized ATP and its preferential use by the Na+/K+-ATPase of human red cell ghosts. J Gen Physiol69:605–632
37.
RaffinCNSickTJRosenthalM, (1988) Prolonged impairment of stimulus-evoked K+ reaccumulation after restoration of basal ion homeostasis following brain ischemia. Fed Proc2:A819
38.
RosenthalMJobsisFF, (1971) Intracellular redox changes in the functioning cerebral cortex. II. Effects of direct cortical stimulation. J Neurophysiol34:750–761
39.
RosenthalMLaMannaJC, (1975) Effects of ouabain and phenobarbital on the kinetics of cortical metabolic transients associated with evoked potentials. J Neurochem24:111–116
40.
RosenthalMLaMannaJCYamadaSYountsBWSomjenGG, (1979) Oxidative metabolism, extracellular potassium and sustained potential shifts in cat spinal cord in situ. Brain Res162:113–127
41.
SickTJRosenthalMLaMannaJCLutzPL, (1982) Brain potassium ion homeostasis during anoxia and metabolic inhibition in the turtle and rat. Am J Physiol243:R281–R288
42.
SiesjoBK, (1978) Brain Energy Metabolism. New York, John Wiley & Sons
43.
SylviaALRosenthalM, (1978) The effect of age and lung pathology on cytochrome a,a,3 redox levels in rat cerebral cortex. Brain Res146:109–122
44.
UrbanicsRLeniger-FollertELubbersDW, (1978) Time course of changes of extracellular H+ and K+ activities during and after direct electrical stimulation of the brain cortex. Pflugers Arch378:47–53
45.
VannucciRCNardisEEVannucciSJCampbellPA, (1981) Cerebral carbohydrate and energy metabolism during hypoglycemia in newborn dogs. Am J Physiol240:R192–R199
