Actions of dinitrophenol and some other metabolic inhibitors on cortical neurones

Godfraind, Jean‐Marie; Kawamura, Hiroé; Krnjević, K.; Pumain, R.

doi:10.1113/jphysiol.1971.sp009465

Cited by 135 publications

(47 citation statements)

References 36 publications

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“…Since these data are measurements of dependent variables over time, analysis of variance (ANOVA) for a 2-factor experiment with repeated measures on 1 factor 12 was applied to 3 portions of the data: the hypoxic period (defined as minutes 0-30), the early recovery period (minutes [31][32][33][34][35][36][37][38][39][40][41], and the late recovery period (minutes 45-70). To perform this analysis and assess only changes due to hypoxia independent from the prehypoxic state of different slices, ion and potential data in each experiment were normalized to the average of 3 prehypoxic readings.…”

Section: Methodsmentioning

confidence: 99%

The effect of graded hypoxia on the hippocampal slice: an in vitro model of the ischemic penumbra.

Schiff¹,

Somjen²

1987

Stroke

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Submerged hippocampal slices were exposed to 30 minutes of moderate or mild hypoxia at 29°C and then reoxygenated. Synaptic transmission was lost at the same rate in response to either grade of hypoxia, but recovery was faster following mild hypoxia. Hyperexcitability of synaptic transmission was a lasting feature following moderate hypoxia, but it was transient following mild hypoxia; after mild hypoxia the strength of synaptic transmission eventually returned to normal. Extracellular calcium did not change during moderate hypoxia. The extracellular pH of slices was always more acid than the bath; pH decreased further in response to both moderate and mild hypoxia. Extracellular potassium increased more during moderate than during mild hypoxia, and a period of rapid potassium uptake was also more pronounced following moderate hypoxia. Extracellular DC potential demonstrated a small positive shift during hypoxia, more so during mild hypoxia. These experiments suggest that synaptic function can be reversibly suppressed in mildly hypoxic brain tissue without severe depolarization of neurons; in addition, the degree and duration of posthypoxic hyperexcitability are correlated with the degree of hypoxia and the magnitude of the release of K+ from cells into their environment. (Stroke 1987;18:30-37) A GROWING body of evidence suggests that / \ neuronal activity is suppressed by ischemia A. A . before the structural integrity of neurons is lost. How long neurons can exist in such an inactive state before irreversible damage occurs depends on the degree and duration of blood flow reduction 1 and the specific vulnerability to ischemia of individual neurons. 2Following complete occlusion of a cerebral vessel, a gradient of flow exists: from near or total cessation of flow in the central area of a vessel's territory of distribution to normal or increased flow at the periphery of the territory.3 It has been postulated that there exists a region where blood flow is reduced to levels where cerebral functions (electroencephalogram and evoked potentials) are suppressed but ion homeostasis is mostly preserved -the "ischemic penumbra."4 That areas of reduced flow consistent with an ischemic penumbra exist in human stroke patients is known, 3 but whether such tissue is capable of regaining full function on resumption of normal oxygen delivery cannot be determined from available information. Indeed, whether an ischemic penumbra exists as originally conceived has aroused considerable controversy. 3Ischemia is a complex insult consisting of impaired oxygen and glucose delivery and impaired metabolic waste removal. It is difficult to investigate how graded changes in one variable of ischemia, such as hypoxia, affect the brain in situ because of accompanying vascular and other systemic responses. The thin in vitro Received November 27, 1985; accepted July 2, 1986. brain slice therefore provides a practical method to study the effect of hypoxia on the physiology of functioning neural tissue. We have previously shown that synaptic tra...

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Section: Methodsmentioning

confidence: 99%

The effect of graded hypoxia on the hippocampal slice: an in vitro model of the ischemic penumbra.

Schiff¹,

Somjen²

1987

Stroke

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“…The electrode coupling resistance was balanced out with a bridge circuit when the electrode was in an extracellular position (cf. Araki & Otani, 1955;Frank & Fuortes, 1956;Godfraind et al 1971 K. KRNJE VIC AND A. LISIEWICZ Fig. 6 illustrates the changes in resistance recorded inside a motoneurone during an injection of Ca2 .…”

Section: Change In Membrane Re8itancementioning

confidence: 99%

“…But if slower mitochondrial activity allows the internal free Ca2+ level to rise, neuronal firing would be damped down. This may well be the mechanism of the reversible hyperpolarization and fall in excitability that are observed in the cerebral cortex during hypoxia (Glotzner, 1967;Godfraind et al 1971).…”

Section: Signifitarce Of Observationsmentioning

confidence: 99%

Injections of calcium ions into spinal motoneurones

Krnjević¹,

Lisiewicz²

1972

The Journal of Physiology

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272

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SUMMARY1. In cats under Dial anaesthesia, Ca2+ was injected inside lumbosacral motoneurones, by passing currents between CaCl2-and KCl-containing barrels of compound micropipettes.2. There was a reduction in excitability and a fall in membrane resistance, both rapid in onset and quickly reversible. 4. The most common change in membrane potential was a hyperpolarization; but in nearly half the cases, there was no clear change or a small depolarization. A reversal level for the effect of Ca2+ could be measured in five cells: on the average, it was 10 mV more negative than the resting potential.5. Observations on i.p.s.p.s showed that Ca2+ probably does not alter gC: it was concluded that the fall in membrane resistance caused by intracellular Ca2+ is mainly due to an increase in gK.6. These results confirm previous suggestions that a steep transmembrane gradient of Ca2+ is essential for the maintenance of a low membrane conductivity, and that a rise in internal free Ca2+ -whether due to influx or release from internal stores -may play an important role in regulating neuronal activity.

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“…This has been observed during hypoxia [5][6][7]10] as well as during glucose depletion [14]. The controlling substance which links cellular metabolism and K ÷ conductance is still subject of discussion.…”

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confidence: 99%

Adenosine, ‘pertussis-sensitive’ G-proteins, and K+ conductance in central mammalian neurones under energy deprivation

Spuler¹,

Grafe²

1989

Neuroscience Letters

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There is a striking similarity between the effects of adenosine and of hypoxia or glucose depletion on membrane potential and conductance of hippocampal neurones in tissue slices of rat brain. Both induce a membrane hyperpolarization by an increase in potassium conductance. It seemed likely, therefore, that a rise in extracellular adenosine concentration during energy deprivation may link neuronal metabolism with membrane K ÷ conductance. To test this hypothesis, we have now investigated the effects of hypoxia/ glucose deprivation on hippocampal neurones from pertussis toxin-treated rats. In such slices adenosine had no effect on postsynaptic membrane potential and input resistance. Nevertheless, hypoxia or glucose depletion were as effective as in controls. These data provide evidence against adenosine as the main mediator between cell metabolism and potassium conductance.An early effect of energy deprivation in central mammalian neurones is an increase in membrane K + conductance. This has been observed during hypoxia [5][6][7]10] as well as during glucose depletion [14]. The controlling substance which links cellular metabolism and K ÷ conductance is still subject of discussion. It has been discussed that adenosine may be such a mediator [9] since adenosine induced an increase in neuronal K ÷ conductance [8,12,13] in electrophysiological studies on mammalian brain slices. Furthermore, the content of this purine increases in brain tissue under energy deprivation [3,4,9]. However, so far this hypothesis has not been adequately explored. In our experiments we made use of the knowledge that adenosine receptors are linked to K ÷ channels via pertussis toxin (PTX)-sensitive G-proteins [11]. Therefore, hypoxia and glucose deprivation were explored on PTX-treated rats.The experiments were performed on transverse slices (500/tm thick) or rat (250-300 g) hippocampus. The slices were kept totally immersed in an experimental chamber perfused with an oxygenated solution containing (in mM); NaCI 118, KCI

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Actions of dinitrophenol and some other metabolic inhibitors on cortical neurones

Cited by 135 publications

References 36 publications

The effect of graded hypoxia on the hippocampal slice: an in vitro model of the ischemic penumbra.

The effect of graded hypoxia on the hippocampal slice: an in vitro model of the ischemic penumbra.

Injections of calcium ions into spinal motoneurones

Adenosine, ‘pertussis-sensitive’ G-proteins, and K+ conductance in central mammalian neurones under energy deprivation

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