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

This study was directed at relating ion transport 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+o. Moderate hypoxia (Pao2 above 50 mm Hg) resulted in reduction of cytochrome a,a3 but only slight elevation of K+o. At this level of hypoxia, cytochrome a,a3 continued to respond to neuronal activation with transient shifts toward oxidation and rates of K+o reaccumulation were unchanged from control. When Pao2 was further decreased below a critical threshold, stimulus-provoked oxidative responses of 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+o without provocation of spreading cortical depression. These data indicate that ion transport activity in cerebral cortex is more refractory to hypoxia than is mitochondrial redox functioning. They suggest an in vivo parallel to the “cushioning” effect of mitochondria in vitro, in which oxygen consumption remains constant despite fluctuations in oxygenation 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.

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Inhibition of Glycolysis Alters Potassium Ion Transport and Mitochondrial Redox Activity in Rat Brain

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.1988.143 ◽

1988 ◽

Vol 8 (6) ◽

pp. 857-865 ◽

Cited By ~ 24

Author(s):

Cesar N. Raffin ◽

Thomas J. Sick ◽

Myron Rosenthal

Keyword(s):

Ion Transport ◽

Iodoacetic Acid ◽

Potassium Ion ◽

Redox Activity ◽

Extracellular Potassium ◽

Potassium Ion Transport ◽

Ion Activity ◽

Inhibition Of Glycolysis ◽

Glycolytic Inhibitor ◽

Active Processes

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.

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Brain potassium ion homeostasis, anoxia, and metabolic inhibition in turtles and rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1982.243.3.r281 ◽

1982 ◽

Vol 243 (3) ◽

pp. R281-R288 ◽

Cited By ~ 8

Author(s):

T. J. Sick ◽

M. Rosenthal ◽

J. C. LaManna ◽

P. L. Lutz

Keyword(s):

Rat Brain ◽

Oxygen Tension ◽

Ion Homeostasis ◽

High Energy ◽

Potassium Ion ◽

Tissue Oxygen Tension ◽

Extracellular Potassium ◽

Tissue Oxygen ◽

Cytochrome Aa3 ◽

The Brain

Microelectrode measurements of tissue oxygen tension (PtO2) and extracellular potassium ion concentration ([K+]o) and dual wavelength spectrophotometric measurements of the reduction/oxidation state of cytochrome aa3 were used to compare the resistance of turtle and rat brain to anoxia in vivo. In both species, respiration with 100% N2 resulted in a decrease of tissue oxygen tension to near 0 mmHg and reduction of cytochrome aa3. However, N2 respiration resulted in only moderate elevation of [K+]o in turtle bran while [K+]o in rat brain was elevated to levels greater than 50 mM. In addition, N2 respiration in turtles had no effect on the rate of recovery of [K+]o, which was elevated by direct electrical stimulation of the brain. Electrocorticographic activity (ECoG) of the turtle brain was only moderately depressed during N2 respiration for up to 4 h whereas the ECoG of rat brain became isoelectric within 1 min. Inhibition of glycolysis with iodoacetate (IAA) resulted in rapid elevation of [K+]o in turtle brain during anoxia, but IAA had little effect on [K+]o during normoxia. These results indicate that the remarkable resistance of the diving turtle to anoxia does not result from continued provision of oxygen to the brain either by redistribution of systemic blood flow or from blood O2 storage. In addition, the turtle brain does not rely on cellular stores of high-energy compounds for maintenance of ionic homeostasis. We conclude that potassium ion homeostasis in the anoxic turtle brain must result from increased glycolytic ATP production and from decreased energy utilization.

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Changes in Extracellular Calcium Activity in Cerebral Ischaemia

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.1981.21 ◽

1981 ◽

Vol 1 (2) ◽

pp. 203-209 ◽

Cited By ~ 297

Author(s):

Robert J. Harris ◽

Lindsay Symon ◽

Neil M. Branston ◽

Muzaffer Bayhan

Keyword(s):

Blood Flow ◽

Cerebral Cortex ◽

Ion Homeostasis ◽

Extracellular Potassium ◽

Energy Reserves ◽

Local Cerebral Blood Flow ◽

Cellular Energy ◽

Dramatic Rise ◽

Ion Sensitive Microelectrodes ◽

Ion Activities

Changes in extracellular ion activities were measured during partial ischaemia of the cerebral cortex of primates anaesthetised with α-chloralose. Triple-barrelled, double-ion-sensitive microelectrodes were used to measure the extracellular potassium (Ke) and calcium (Cae) activity at the same point simultaneously. The ion changes were related to local cerebral blood flow, and it was shown that at a blood flow of approximately 10 ml 100 g−1 min−1, there is a threshold below which ion homeostasis is disturbed. This is associated with a dramatic rise in Ke and fall in Cae. Cae falls from a normal value of 1.31 ± 0.1 mm to approximately 0.28 mm in densely ischaemic tissue. In ischaemia, Ke reaches 13.4 ± 3.8 mm before Cae begins to fall. The fall in Cae, although related to reduced blood flow, is closely associated with and follows the rise in Ke. The change in Cae is probably due to an increase in membrane permeability, as a result of either depolarisation or a critical lowering of cellular energy reserves.

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A Comparison of the Effects of Ischaemia on Tissue Flow, Electrical Activity and Extracellular Potassium Ion Concentration in Cerebral Cortex of Baboons

Biochemical Society Transactions ◽

10.1042/bst0050158 ◽

1977 ◽

Vol 5 (1) ◽

pp. 158-160 ◽

Cited By ~ 10

Author(s):

ANTHONY J. STRONG ◽

MICHELE J. GOODHARDT ◽

NEIL M. BRANSTON ◽

LINDSAY SYMON

Keyword(s):

Cerebral Cortex ◽

Electrical Activity ◽

Potassium Ion ◽

Ion Concentration ◽

Extracellular Potassium

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Glycolytic and oxidative metabolic contributions to potassium ion transport in rat cerebral cortex

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y92-258 ◽

1992 ◽

Vol 70 (S1) ◽

pp. S165-S169 ◽

Cited By ~ 24

Author(s):

Myron Rosenthal ◽

Thomas J. Sick

Keyword(s):

Cerebral Cortex ◽

Oxidative Phosphorylation ◽

Extracellular Space ◽

Early Period ◽

High Energy ◽

Potassium Ion ◽

Rat Cerebral Cortex ◽

Extracellular Potassium ◽

Rapid Phase ◽

Atp Pool

Putative roles of glycolytic and oxidative metabolism in the removal of potassium ion from the extracellular space were examined in rat cerebral cortex. In response to direct electrical stimulation of the cerebral surface, the activity of extracellular potassium ion [Formula: see text] transiently increased. Inhibition of glycolysis with iodoacetate prolonged the time required for dissipation of the elevated [Formula: see text]. This slowing was most evident in the early period after stimulation, when [Formula: see text] was relatively high. Levels of high-energy intermediates were unchanged by iodoacetate. In contrast, severe hypoxemia was without effect during the early phase of K+ removal but hypoxemia slowed the later restoration of the [Formula: see text] baseline. These data demonstrate that the rapid removal of potassium ion from the extracellular space following intense neuronal activity is aided by the Embden–Myerhoff metabolic pathways and perhaps by direct coupling of ATP produced by glycolysis. We suggest that removal of potassium ion from the brain extracellular space depends on two ATP pools, one derived from oxidative phosphorylation, the other from glycolysis. The glycolytic ATP pool may be most involved in the early and rapid phase of potassium clearance; the oxidative ATP pool may be more associated with the second and slower phase of [Formula: see text] clearance, and with the maintenance of the [Formula: see text] baseline under 'resting' conditions.Key words: potassium, glycolysis, oxidative phosphorylation, hypoxemia, iodoacetate.

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Evidence for an Aspartyl Phosphate Residue at the Active Site of Sodium and Potassium Ion Transport Adenosine Triphosphatase

Journal of Biological Chemistry ◽

10.1016/s0021-9258(19)43350-4 ◽

1973 ◽

Vol 248 (20) ◽

pp. 6993-7000 ◽

Cited By ~ 3

Author(s):

Robert L. Post ◽

Shoji Kume

Keyword(s):

Ion Transport ◽

Active Site ◽

Adenosine Triphosphatase ◽

Potassium Ion ◽

Potassium Ion Transport ◽

Sodium And Potassium

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BMP signaling alters aquaporin-4 expression in the mouse cerebral cortex

Scientific Reports ◽

10.1038/s41598-021-89997-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Kazuya Morita ◽

Naoyuki Matsumoto ◽

Kengo Saito ◽

Toshihide Hamabe-Horiike ◽

Keishi Mizuguchi ◽

...

Keyword(s):

Cerebral Cortex ◽

Molecular Mechanisms ◽

Water Movement ◽

Water Channel ◽

Bmp Signaling ◽

Aquaporin 4 ◽

Mammalian Brain ◽

Physiological Conditions ◽

Pathological Conditions ◽

Mouse Cerebral Cortex

AbstractAquaporin-4 (AQP4) is a predominant water channel expressed in astrocytes in the mammalian brain. AQP4 is crucial for the regulation of homeostatic water movement across the blood–brain barrier (BBB). Although the molecular mechanisms regulating AQP4 levels in the cerebral cortex under pathological conditions have been intensively investigated, those under normal physiological conditions are not fully understood. Here we demonstrate that AQP4 is selectively expressed in astrocytes in the mouse cerebral cortex during development. BMP signaling was preferentially activated in AQP4-positive astrocytes. Furthermore, activation of BMP signaling by in utero electroporation markedly increased AQP4 levels in the cerebral cortex, and inhibition of BMP signaling strongly suppressed them. These results indicate that BMP signaling alters AQP4 levels in the mouse cerebral cortex during development.

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