The dependence of the respiration of brain cortex on active cation transport

Whittam, R.

doi:10.1042/bj0820205

Cited by 193 publications

(55 citation statements)

References 24 publications

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“…This is about 42 % of the resting 02 consumption at 240 C (Larrabee, 1958) (111 eumole (g dry weight)-' hr-' = 0-31 mole. (g wet weight)-' min-), a proportion in line with previous calculations in isolated brain tissue (Whittam, 1962;Keesey & Wallgren, 1965). After Na loading in carbachol solution the average peak Na efflux rate would correspond to a maximal oxygen consumption rate of 0'57 #mole (g wet weight)-' min-.…”

Section: Discussionsupporting

confidence: 85%

Movements of labelled sodium ions in isolated rat superior cervical ganglia

Brown¹,

Scholfield²

1974

The Journal of Physiology

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SUMMARY1. Isolated rat superior cervical ganglia were incubated in Krebs solution containing 24Na and carbachol for 4 min at 250 C. They were then washed at 30 C for 15 min to remove extracellular 24Na and the efflux of residual intracellular 24Na stimulated by warming to 250 C.2. During the 15 min wash at 30 C desaturation curves became exponential with a rate constant of 0-012 + 0 001 min-' (n = 24). This was assumed to represent loss of intracellular 2MNa, and initial uptake of 24Na was calculated therefrom by back-extrapolation to zero wash-time. After 4 min in 24Na + 180,u/M carbachol intracellular [24Na] so calculated was 61-6 + 341 mM (n = 18), representing 83 % labelling of intracellular Na.In the absence of carbachol intracellular [24Na] was 10-0 + 0-5 mM, representing 49 % labelling. Extracellular Na was labelled by > 90 % after 4 min in "Na. The apparent rate constant for washout of extracellular 2ANa was 0-6 min-' at 30 C and 0-95 min-' at 250 C.3. The loss of the residual intracellular 2MNa during temperature stimulation was interpreted quantitatively in terms of an exponential decline of the bulk of intracellular 24Na with an extrusion rate constant of 0-39 + 0-1 min-' (n = 18), efflux being delayed by passage through the extracellular space with an effective rate constant of 0-8-1-2 min-. 8. The properties of the ganglionic Na pump deduced from rates of temperature-stimulated 2MNa extrusion accord with the view that the ganglion hyperpolarization observed after Na loading by exposure to nicotinic depolarizing agents results from electrogenic Na extrusion. A comparable hyperpolarization is observed after temperature stimulation following Na loading.

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Section: Discussionsupporting

confidence: 85%

Movements of labelled sodium ions in isolated rat superior cervical ganglia

Brown¹,

Scholfield²

1974

The Journal of Physiology

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“…Both of these measurements gave consistent results and showed that glucose and O 2 consumption decreased by 50--60% from that in conscious animals; pento barbital, halothane, or nitrous oxide anesthesia alone inhibit energy metabolism by 20-30%. This value agrees well with the reduction in oxygen con sumption in slices of brain treated with ouabain or incubated in Na + -free solutions (Whittam, 1962), and with declines in oxidative activity of nonmyeli nated nerves treated with ouabain (Ritchie, 1967). Such a large reduction in cerebral O 2 uptake when ion movements are blocked indicates that these pro cesses consume the major portion of cerebral A TP production.…”

Section: How Is the Utilization Of Atp Distributed Among The Various supporting

confidence: 83%

ATP and Brain Function

Erecińska

Silver

1989

J Cereb Blood Flow Metab

750

400

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The importance of A TP as the main source of chemical energy in living matter and its involve ment in cellular processes has long been recog nized. The primary mechanism whereby higher or ganisms, including humans, generate ATP is through mitochondrial oxidative phosphorylation. For the majority of organs, the main metabolic fuel is glucose, which in the presence of oxygen under goes complete combustion to CO 2 and H 2 0:The free energy (.:lG) liberated in this exergonic re action is partially trapped as ATP in two consecu tive processes: glycolysis (cytosol) and oxidative phosphorylation (mitochondria). The first produces 2 mol of ATP per mol of glucose, and the second 36 mol of ATP per mol of glucose. In the latter case, 6 mol of ATP are contributed from the oxidation of 2 mol of NADH generated in the cytosol during gly colysis and transferred into the mitochondria indi rectly through various "shuttle" systems. (In the a-glycerophosphate shuttle, the yield of ATP per NADH is reduced from 3 to 2 because the relevant mitochondrial dehydrogenase is a flavoprotein linked enzyme). Thus, oxidative phosphorylation yields 17-18 times as much useful energy in the form of ATP as can be obtained from the same amount of glucose by glycolysis alone. It is there fore not surprising that limitation of O 2 supply pro duces very damaging effects on cellular function. The brain is one of the organs that is particularly sensitive to lack of oxygen and in humans at rest is responsible for 20% of total O 2 consumption al though it accounts for only 2% of the body weight. in the function of the CNS? It will become evident from our discussion that only partial an swers to these questions are currently available. However, the search for these solutions involves some of the most exciting areas of contemporary neurochemistry. CONCENTRA nONS OF HIGH ENERGY PHOSPHATE COMPOUNDS IN MAMMALIAN BRAINBrain, like all other organs in the body, contains phosphorylated nucleotides that yield energy upon hydrolysis of their phosphate bond(s); the most im portant of these is the adenine nucleotide ATP. In addition, the CNS, in common with other excitable tissues, possesses another high energy reservoir, the creatine phosphate/creatine (PCr/Cr) system,

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“…The former is unlikely since many investigators have shown that passive diffusion of K + contributes insignificantly to the maintenance of brain ion homeostasis and that the major fraction of brain energy consumption is expended to main tain transmembrane cation gradients (Whittam, 1962;Astrup, 1982). Rather, these data suggest that there is greater capacity for anaerobic glycolysis to provide energy for ion homeostasis than has been appreciated previously.…”

Section: Discussionmentioning

confidence: 92%

Potassium Ion Homeostasis and Mitochondrial Redox Activity in Brain: Relative Changes as Indicators of Hypoxia

Milito

Raffin

Rosenthal

et al. 1988

J Cereb Blood Flow Metab

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Summary: This study was directed at relating ion trans port and mitochondrial redox activity during hypoxia, as a step toward definition of brain oxygen sufficiency. To accomplish this, extracellular potassium ion activity (K+o) was recorded by ion-selective microelectrodes while reduction/oxidation (redox) ratios of cytochrome oxidase (cytochrome a,a3) were monitored by reflection spectrophotometry in cerebral cortex of rats anesthetized with pentobarbital. In normoxia, neuronal activation by direct cortical stimulation produced transient oxidation of cytochrome a,a3 and elevation of K +0. Moderate hyp oxia (Pao2 above 50 mm Hg) resulted in reduction of cy tochrome a,a3 but only slight elevation of K +0. At this level of hypoxia, cytochrome a,a3 continued to respond to neuronal activation with transient shifts toward oxida tion and rates of K + 0 reaccumulation were unchanged from control. When Pao2 was further decreased below a critical threshold, stimulus-provoked oxidative responsesMaintenance of brain oxygenation is critical for normal function, ion homeostasis, and cell survival. Early consequences of brain anoxia include rapid reduction of the mitochondrial electron carriers, depression of synaptic transmission, loss of EEG activity and consciousness, and a slow increase in extracellular potassium ion activity (K +0). Subse quent to these changes, a K + 0 threshold is reached at which there are large increases in membrane conductances, maximal K + efflux, and anoxic de polarization (e.g., Chance et aI., 1962; Vyskocil et aI., 1972;Siesj6, 1978;Blass and Gibson, 1979;Hansen, 1985). 155of mitochondrial reactants were replaced by shifts toward reduction, but rates of reaccumulation of K + , spilled into the extracellular space by neuronal activation, remained unchanged. Only during severe hypoxia (Pao2 less than 20 mm Hg) was it possible in some animals to record a slowing in the reaccumulation of K + 0 without provoca tion of spreading cortical depression. These data indicate that ion transport activity in cerebral cortex is more re fractory to hypoxia than is mitochondrial redox func tioning. They suggest an in vivo parallel to the "cushion ing" effect of mitochondria in vitro, in which oxygen consumption remains constant despite fluctuations in ox ygenation and redox ratios, and also that there may be a greater anaerobic capacity to provide energy for ion transport in mammalian brain than has previously been appreciated. K ey Words: Brain oxygenation-Cy tochrome oxidase-Hypoxia-Mitochondria-Potas sium -Spectrophotometry.It remains difficult, however, to define brain ox ygen sufficiency in physiological terms. In part, this is due to the difficulty in extrapolating effects of anoxia to those produced by hypoxia because anoxia-induced changes occur so rapidly and be cause hypoxia-induced alterations do not reach maxima. Also, little is known of the relationships between brain metabolism and ion transport during hypoxia since high-energy intermediates are rela tively unchanged, at least by mild hypoxia (Si...

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The dependence of the respiration of brain cortex on active cation transport

Cited by 193 publications

References 24 publications

Movements of labelled sodium ions in isolated rat superior cervical ganglia

Movements of labelled sodium ions in isolated rat superior cervical ganglia

ATP and Brain Function

Potassium Ion Homeostasis and Mitochondrial Redox Activity in Brain: Relative Changes as Indicators of Hypoxia

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