K + induced stimulation of oxygen uptake in cultured cerebral glial cells

Hertz, Leif; Dittmann, L.; Mandel, P.

doi:10.1016/0006-8993(73)90814-7

Cited by 67 publications

(14 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Elevated extracellular K ϩ concentrations cause a smaller stimulation (ϳ20%) of [ 14 C]DG phosphorylation and glucose oxidation in astrocytes, an effect that appears to be a result of stimulation of Na ϩ , K ϩ -ATPase activity at its extracellular, K ϩ -sensitive site and reaches its maximum at ϳ12 mM K ϩ , a concentration that also causes maximal activity of the Na ϩ , K ϩ -ATPase Peng et al, 1994Peng et al, , 1996Huang et al, 1994;Hajek et al, 1996). In addition, relatively high K ϩ concentrations stimulate oxygen consumption and glucose oxidation in astrocytes transiently (Hertz, 1966;Hertz et al, 1973Hertz et al, , 1998bHertz and Hertz, 1979), a stimulation that probably results from activation of a cotransport system leading to net entry of K ϩ and Cl Ϫ into the cells (Hertz, 1986;Hertz and Dienel, 2002); this cotransporter is activated by a depolarization-induced increase in free cytosolic Ca 2ϩ concentration (Su et al, 2000). Thus, both in glutamatergic neurons and in astrocytes, the metabolic effects of elevated K ϩ are primarily associated with stimulation of ion transport, a conclusion in good agreement with evidence that the increased energy demand during brain activation largely reflects the metabolic demands of increased ion transport (Mata et al, 1980) following the increase in intraneuronal Na ϩ concentration and in extra- right), whereas the same stimulus increased CMR glc by 60%.…”

Section: In Vitro Techniquesmentioning

confidence: 99%

Glucose and lactate metabolism during brain activation

Dienel

Hertz

2001

J of Neuroscience Research

Self Cite

291

285

View full text Add to dashboard Cite

The dependence of brain function on blood glucose as a fuel does not exclude the possibility that lactate within the brain might be transferred between different cell types and serve as an energy source. It has been recently suggested that 1) about 85% of glucose consumption during brain activation is initiated by aerobic glycolysis in astrocytes, triggered by demand for glycolytically derived energy for Na+ -dependent accumulation of transmitter glutamate and its amidation to glutamine, and 2) the generated lactate is quantitatively transferred to neurons for oxidative degradation. However, astrocytic glutamate uptake can be fueled by either glycolytically or oxidatively derived energy, and the extent to which "metabolic trafficking" of lactate might occur during brain function is unknown. In this review, the potential for an astrocytic-neuronal lactate flux has been estimated by comparing rates of glucose utilization in brain and in cultured neurons and astrocytes with those for lactate release and uptake. Working brain tissue and isolated brain cells release large amounts of lactate. Cellular lactate uptake occurs by carrier-mediated facilitated diffusion and is normally limited by its dependence on metabolism of accumulated lactate to maintain a concentration gradient. The rate of this process is similar in cultured astrocytes and glutamatergic neurons, and, at physiologically occurring lactate concentrations, lactate uptake corresponds at most to 25% of the rate of glucose oxidation, which accordingly is the upper limit for "metabolic trafficking" of lactate. Because of a larger local release than uptake of lactate and the necessity for rapid lactate clearance to maintain the intracellular redox state to support lactate production in the presence of normal oxygen levels, brain activation in vivo is probably, in many cases, accompanied by a substantial overflow of glycolytically generated lactate, both to different brain areas and under some conditions (spreading depression, hyperammonemia) to circulating blood.

show abstract

Section: In Vitro Techniquesmentioning

confidence: 99%

Glucose and lactate metabolism during brain activation

Dienel

Hertz

2001

J of Neuroscience Research

Self Cite

291

285

View full text Add to dashboard Cite

show abstract

“…Relevant aspects of glucose metabolism in neurons and astrocytes are illustrated in Figure 15 and described in more detail in its legend. Highly elevated K + concentrations (>15–20 mM) have repeatedly been found to cause large, but transient increases in rate of oxygen consumption in brain slices (Ashford and Dixon, 1935; Dickens and Greville, 1935; Hertz and Schou, 1962), freshly dissected glial cells (Hertz, 1966; Aleksidze and Blomstrand, 1969) or cultured astrocytes (Hertz et al, 1973). The K + concentrations used, and shown to be necessary for the response in brain slices, have generally been those now known to stimulate NKCC1 (Hertz et al, 2004).…”

Section: Comparison Between Effects On Energy Metabolism By K+/na+ Trmentioning

confidence: 99%

“…K + concentrations of 10–12 mM stimulate glycolysis in cultured astrocytes, with >80% of the stimulation evoked by a rise in extracellular K + concentration from 5.4 to 12 mM being inhibited in the presence of 10 mM ouabain (Peng et al, 1996). Higher K + concentrations increase oxidative glucose metabolism in cultured astrocytes (Hertz et al, 1973). …”

Section: Comparison Between Effects On Energy Metabolism By K+/na+ Trmentioning

confidence: 99%

Astrocytic and neuronal accumulation of elevated extracellular K+ with a 2/3 K+/Na+ flux ratio—consequences for energy metabolism, osmolarity and higher brain function

Hertz¹,

Xu²,

Song³

et al. 2013

Front. Comput. Neurosci.

Self Cite

View full text Add to dashboard Cite

Brain excitation increases neuronal Na+ concentration by 2 major mechanisms: (i) Na+ influx caused by glutamatergic synaptic activity; and (ii) action-potential-mediated depolarization by Na+ influx followed by repolarizating K+ efflux, increasing extracellular K+ concentration. This review deals mainly with the latter and it concludes that clearance of extracellular K+ is initially mainly effectuated by Na+,K+-ATPase-mediated K+ uptake into astrocytes, at K+ concentrations above ~10 mM aided by uptake of Na+,K+ and 2 Cl− by the cotransporter NKCC1. Since operation of the astrocytic Na+,K+-ATPase requires K+-dependent glycogenolysis for stimulation of the intracellular ATPase site, it ceases after normalization of extracellular K+ concentration. This allows K+ release via the inward rectifying K+ channel Kir4.1, perhaps after trans-astrocytic connexin- and/or pannexin-mediated K+ transfer, which would be a key candidate for determination by synchronization-based computational analysis and may have signaling effects. Spatially dispersed K+ release would have little effect on extracellular K+ concentration and allow K+ accumulation by the less powerful neuronal Na+,K+-ATPase, which is not stimulated by increases in extracellular K+. Since the Na+,K+-ATPase exchanges 3 Na+ with 2 K+, it creates extracellular hypertonicity and cell shrinkage. Hypertonicity stimulates NKCC1, which, aided by β-adrenergic stimulation of the Na+,K+-ATPase, causes regulatory volume increase, furosemide-inhibited undershoot in [K+]e and perhaps facilitation of the termination of slow neuronal hyperpolarization (sAHP), with behavioral consequences. The ion transport processes involved minimize ionic disequilibria caused by the asymmetric Na+,K+-ATPase fluxes.

show abstract

“…Because cesium is able to utilize a potassium carrier (at least in erythrocytes), this strongly suggests that the potassium-induced stimulation of oxygen uptake and swelling likewise represent an active uptake of potassium plus chloride. Both the potassium-induced swelling [Gerschenfeld et al, 1959;M6ller et al, 19741 and the enhancement of oxygen uptake [Hertz, 1966;Hertz et al, 1973;Hertz and Hertz, 19791 occur in astrocytes, and a potassium-stimulated chloride uptake has been observed in an astrocytic cell line [Gill et al, 19741. A recent finding of a potassium uptake into astrocytes in primary cultures, which is inhibited by furosemide (i.e., occurs together with chloride) and operates only at elevated potassium concentration [Walz and Hertz, 19841, therefore, gives further support to the present conclusion.…”

Section: Discussionmentioning

confidence: 99%

Functional role of the potassium‐induced stimulation of oxygen uptake in brain slices studied with cesium as a probe

Hertz

Kjeldsen

1985

J of Neuroscience Research

View full text Add to dashboard Cite

The potassium-induced stimulation of oxygen consumption in brain slices has a threshold value of 15-20 mM potassium, and it reaches its maximum at 35-50 mM. Although this phenomenon now has been known for almost 50 years, its physiological role remains undetermined. One reason for this may be that the high concentrations of potassium that are required for this response also have many other consequences, e.g., a depolarization of the cells, and that the different effects to some extent may mask each other. For this reason this investigation studied the effects of cesium, which evokes a maximal stimulation of oxygen consumption already at 15 mM. Like potassium, concentrations of cesium that stimulate oxygen consumption also lead to an enhanced swelling. Unlike potassium, the sodium content is affected very little by these concentrations of cesium, whereas cesium and chloride contents are increased. On this basis it is concluded that the cesium-induced stimulation of oxygen uptake is a metabolic manifestation of an active uptake of cesium and chloride, which secondarily leads to an uptake of water, i.e., the cesium-induced swelling. Analogously, it is suggested that the potassium-induced stimulation of oxygen uptake represents an active accumulation of potassium and chloride.

show abstract

K + induced stimulation of oxygen uptake in cultured cerebral glial cells

Cited by 67 publications

References 14 publications

Glucose and lactate metabolism during brain activation

Glucose and lactate metabolism during brain activation

Astrocytic and neuronal accumulation of elevated extracellular K+ with a 2/3 K+/Na+ flux ratio—consequences for energy metabolism, osmolarity and higher brain function

Functional role of the potassium‐induced stimulation of oxygen uptake in brain slices studied with cesium as a probe

Contact Info

Product

Resources

About