Ceiling of stimulus induced rises in extracellular potassium concentration in the cerebral cortex of cat

Heinemann, Uwe; Lux, H. D.

doi:10.1016/0006-8993(77)90903-9

Cited by 342 publications

(180 citation statements)

References 38 publications

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“…The ob served difference in the metabolic and hemody- '-!---T� are reversed only during the action potentials. However, some extracellular accumulation of po tassium may occur during intense stimulation, but levels will increase < 1 mmollL (Heinemann and Lux, 1977). Therefore, energy is consumed mainly by the neuronal Na, K-ATPase and for the active removal of the slightly elevated potassium from the extracellular space (Cordingley and Somjen, 1978).…”

Section: Discussionmentioning

confidence: 99%

Metabolic and Hemodynamic Activation of Postischemic Rat Brain by Cortical Spreading Depression

Köcher

1990

J Cereb Blood Flow Metab

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Summary: Following transient ischemia of the brain, the coupling between somatosensory activation and the he modynamic-metabolic response is abolished for a certain period despite the partial recovery of somatosensory evoked responses. To determine whether this disturbance is due to alterations of the stimulus-induced neuronal ex citation or to a breakdown of the coupling mechanisms, cortical spreading depression was used as a metabolic stimulus in rats before and after ischemia. Adult rats were subjected to 30 min of global forebrain ischemia and 3-6 h of recirculation. EEG, cortical direct current (DC) po tential, and laser-Doppler flow were continuously re corded. Local CBF (LCBF), local CMR g lc (LCMR g1 c), regional tissue contents of ATP, glucose, and lactate, and regional pH were determined by quantitative autoradiog raphy, substrate-induced bioluminescence, and fluorom etry. Amplitude and frequency of the DC shifts did not differ between groups. In control animals, spreading de pression induced a 77% rise in cortical glucose consump tion, a 66% rise in lactate content, and a drop in tissue pH of 0.3 unit. ATP and glucose contents were not depleted.If cerebral global ischemia exceeds 10 min, long lasting impairment of neurological function will re sult. In the four-vessel occlusion model in rats that allows long-term survival after an ischemic impact, disturbances of sensorimotor integration and motor performance persist for at least 2 days (Combs and D' Alecy, 1987), although the supply of energy-rich phosphates is replenished within 1 h (Pulsinelli and Duffy, 1983;Naruse et al. , 1984).It has been suggested that despite the early re covery of energy metabolism, impaired neurologi- 564During the passage of DC shifts, transient increases «2 min) in laser-Doppler flow were observed, followed by a post-spreading depression hypoperfusion. A comparable although less expressed pattern of hemodynamic and metabolic changes was observed in the postischemic rats. Although baseline LCMR g lc was depressed after isch emia, it was activated 47% during spreading depression. Lactate increased by 26%, pH decreased by 0.3 unit, and ATP and glucose remained unchanged. The extent of the transient increase in laser-Doppler flow did not differ from that of the control group, and a post-spreading de pression hypoperfusion was also found. The results dem onstrate that the postischemic brain may, although to a lesser degree, cover additional energy demands. The pre viously observed suppression of functional activation af ter ischemia is probably caused by both alterations in afferent synaptic transmission and subsequent neuronal excitation and the diminution of the metabolic response to a local stimulus as observed during spreading depres sion.

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Section: Discussionmentioning

confidence: 99%

Metabolic and Hemodynamic Activation of Postischemic Rat Brain by Cortical Spreading Depression

Köcher

1990

J Cereb Blood Flow Metab

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“…Yet, the idea that elevated extracellular potassium concentration in the interstitial space is responsible for initiating seizure activity remains controversial. Some have concluded that [K] o is not responsible for the initiation or the termination of the seizure activity (Lux 1974;Moody et al 1974;Fisher et al 1976;Heinemann & Lux 1977;Kager et al 2000;Somjen 2004). Others have shown that [K] o accumulation can initiate seizure activity (Zuckermann & Glaser 1968;Izquierdo et al 1970;O'Connor & Lewis 1974).…”

Section: Computer Simulation Of Lateral Diffusion In Neural Networkmentioning

confidence: 99%

Potassium diffusive coupling in neural networks

Durand

Park

Jensen

2010

Phil. Trans. R. Soc. B

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Conventional neural networks are characterized by many neurons coupled together through synapses. The activity, synchronization, plasticity and excitability of the network are then controlled by its synaptic connectivity. Neurons are surrounded by an extracellular space whereby fluctuations in specific ionic concentration can modulate neuronal excitability. Extracellular concentrations of potassium ([K þ ] o ) can generate neuronal hyperexcitability. Yet, after many years of research, it is still unknown whether an elevation of potassium is the cause or the result of the generation, propagation and synchronization of epileptiform activity. An elevation of potassium in neural tissue can be characterized by dispersion (global elevation of potassium) and lateral diffusion (local spatial gradients). Both experimental and computational studies have shown that lateral diffusion is involved in the generation and the propagation of neural activity in diffusively coupled networks. Therefore, diffusion-based coupling by potassium can play an important role in neural networks and it is reviewed in four sections. Section 2 shows that potassium diffusion is responsible for the synchronization of activity across a mechanical cut in the tissue. A computer model of diffusive coupling shows that potassium diffusion can mediate communication between cells and generate abnormal and/or periodic activity in small ( §3) and in large networks of cells ( §4). Finally, in §5, a study of the role of extracellular potassium in the propagation of axonal signals shows that elevated potassium concentration can block the propagation of neural activity in axonal pathways. Taken together, these results indicate that potassium accumulation and diffusion can interfere with normal activity and generate abnormal activity in neural networks.

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“…Under physiological conditions, Cl Ϫ accumulation would be diminished by the concomitant removal of K ϩ from the extracellular space (Payne, 1997). During epileptiform activity, however, [K ϩ ] o has been found to remain at high levels (10 -12 mM) (Heinemann and Lux, 1977), with the result that the K ϩ -Cl Ϫ transport actually accumulates Cl Ϫ and hence intensifies epileptiform activity. Therefore, furosemide may have some antiepileptic potency under such an experimental condition (Hochman et al, 1995).…”

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A Furosemide-Sensitive K⁺–Cl⁻Cotransporter Counteracts Intracellular Cl⁻Accumulation and Depletion in Cultured Rat Midbrain Neurons

1999

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Efficacy of postsynaptic inhibition through GABA A receptors in the mammalian brain depends on the maintenance of a Cl Ϫ gradient for hyperpolarizing Cl Ϫ currents. We have taken advantage of the reduced complexity under which Cl Ϫ regulation can be investigated in cultured neurons as opposed to neurons in other in vitro preparations of the mammalian brain. GABA is the main inhibitory transmitter in the mammalian brain. The dominant effect of GABA A receptor activation is a hyperpolarization caused by C l Ϫ flux into the cell (for review, see Sivilotti and Nistri, 1991;Kaila, 1994;Thompson, 1994). However, the direction of the C l Ϫ flux depends on the C l Ϫ gradient across the membrane. Indeed, GABA A receptor-mediated hyperpolarizing and /or depolarizing postsynaptic potentials have been observed (for review, see Kaila, 1994;Thompson, 1994). Some findings suggest variations in intracellular [C l Ϫ ] between different neurons and even a distinct C l Ϫ distribution in different compartments of a single neuron (Misgeld et al., 1986). Depolarizing GABA A responses, however, can be caused by bicarbonate efflux in combination with C l Ϫ influx or combined Cl Ϫ and HCO 3 Ϫ efflux (Grover et al., 1993;Kaila, 1994;Thompson, 1994;Staley et al., 1995;Perkins and Wong, 1996;Kaila et al., 1997). To be able to predict the direction of C l Ϫ currents flowing during GABA A receptor-mediated inhibition it is essential to understand the regulation of C l Ϫ homeostasis that provides the transmembrane gradient.A recently cloned K ϩ -Cl Ϫ cotransporter gene (KCC2) represents a perfect candidate for the regulation of neuronal Cl Ϫ homeostasis (Payne et al., 1996). In contrast to the ubiquitous presence of the K ϩ -Cl Ϫ cotransporter KCC1, expression of the K ϩ -Cl Ϫ cotransporter KCC2 is detected in C NS only and seems to be neuron specific. KCC2 is also distinct from KCC1 in that KCC2 is not involved in cell volume regulation and not activated by osmotic changes. Furthermore, KCC2 has a high affinity for extracellular K ϩ ions. The properties of KCC2 allow the regulation of [Cl Ϫ ] i to maintain Cl Ϫ gradients for hyperpolarizing GABAergic inhibition. Thermodynamic considerations predict that the electroneutral K ϩ -Cl Ϫ cotransporter KCC2 operates near equilibrium under physiological ionic conditions. Depending on [Cl Ϫ ] i and [K ϩ ] o (Payne, 1997), the transport will extrude or accumulate Cl Ϫ .The functional role of a particular Cl Ϫ transport system in neuronal Cl Ϫ regulation is difficult to establish in studies using integral preparations such as brain slices. One complicating factor is the presence of HCO 3 Ϫ anions. The HCO 3 Ϫ permeability of the GABA A channel (Bormann, 1988;Fatima-Shad and Barry, 1993) impedes conclusions toward actual [Cl Ϫ ] i if they are calculated from reversal potentials of GABA A receptor-mediated anion currents. Furthermore, a HCO 3 Ϫ /Cl Ϫ exchanger (RaleySusman et al., 1993) may well interfere (Chesler, 1990), and pH changes that result from manipulations of [HCO 3 Ϫ ] o strongly affect neur...

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Ceiling of stimulus induced rises in extracellular potassium concentration in the cerebral cortex of cat

Cited by 342 publications

References 38 publications

Metabolic and Hemodynamic Activation of Postischemic Rat Brain by Cortical Spreading Depression

Metabolic and Hemodynamic Activation of Postischemic Rat Brain by Cortical Spreading Depression

Potassium diffusive coupling in neural networks

A Furosemide-Sensitive K⁺–Cl⁻Cotransporter Counteracts Intracellular Cl⁻Accumulation and Depletion in Cultured Rat Midbrain Neurons

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Ceiling of stimulus induced rises in extracellular potassium concentration in the cerebral cortex of cat

Cited by 342 publications

References 38 publications

Metabolic and Hemodynamic Activation of Postischemic Rat Brain by Cortical Spreading Depression

Metabolic and Hemodynamic Activation of Postischemic Rat Brain by Cortical Spreading Depression

Potassium diffusive coupling in neural networks

A Furosemide-Sensitive K+–Cl−Cotransporter Counteracts Intracellular Cl−Accumulation and Depletion in Cultured Rat Midbrain Neurons

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A Furosemide-Sensitive K⁺–Cl⁻Cotransporter Counteracts Intracellular Cl⁻Accumulation and Depletion in Cultured Rat Midbrain Neurons