Potassium accumulation in interstitial space during epileptiform seizures
TL;DR: There is an increase in the concentration of potassium in the interstitial space during seizures, and a model is proposed in which this potassium accumulation is an important step in the regenerative, all-or-none-aspect of the initiation of seizures.
About: This article is published in Experimental Neurology.The article was published on 1970-03-01 and is currently open access. It has received 211 citations till now. The article focuses on the topics: Water flow & Potassium.
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TL;DR: The characteristics of spreading depression and the related hypoxic SD-like depolarization and the main hypotheses that have been proposed to explain them are reviewed.
Abstract: Spreading depression (SD) and the related hypoxic SD-like depolarization (HSD) are characterized by rapid and nearly complete depolarization of a sizable population of brain cells with massive redi...
1,058 citations
Cites background from "Potassium accumulation in interstit..."
...Analyzing impedance and phase angle at several frequencies, Ranck (316) concluded that, during SD, interstitial space shrinks, neuronal membrane resistance decreases and, a little later, glial membrane resistance increases (see also Ref....
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...“Cathodal block” is synonymous with inactivation [Modified from Fertziger and Ranck (85)....
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TL;DR: A special effort to show how investigations of the epilepsies with methods from diverse disciplines can be complementary and mutually reinforcing and explain how electrophysiologic insights into the mechanisms of seizures induced by high K+ provide a plausible connection between the genotype and phenotype in a familial epilepsy.
Abstract: The epilepsies comprise a remarkably diverse collection of disorders that affect 1% of the population in the United States (Hauser and Hesdorffer, 1990). Current therapy is symptomatic. Available drugs reduce seizure frequency in the majority of patients, but only 40% are free of seizures despite optimal treatment (Elwes et al., 1984; Mattson et al., 1985). Neither an effective prophylaxis nor a cure of any of these disorders is available except neurosurgical resection of epileptic tissue in selected instances. There is hope that understanding the cellular and molecular mechanisms of the epilepsies will lead to improved therapies as well as new insights into brain structure and function. Because of the inherent diversity of the epilepsies and their models and the wide range of techniques used for investigating their cellular and molecular basis, I focused on selected rhodels and issues, attempted to bring some coherency to the findings, and sought to draw conclusions that may be generally relevant to epilepsy. I made a special effort to show how investigations of the epilepsies with methods from diverse disciplines can be complementary and mutually reinforcing. By use of the tools of electrophysiology it was initially demonstrated that the epilepsies are disorders of neuronal excitability, which were subsequently characterized in populations of neurons, in individual neurons, and single ion channels. Advances in molecular biology and molecular genetics have elucidated the molecular mechanism of a familial epilepsy. I have attempted to show how these diverse approaches can be mutually reinforcing and explain how electrophysiologic insights into the mechanisms of seizures induced by high K+ provide a plausible connection between the genotype and phenotype in a familial epilepsy. Throughout my account I have addressed the potential therapeutic implications of discerning the underlying mechanisms. The first topic considered is the terminology and classification of epileptic seizures. Next, I address the cellular mechanisms of seizures induced in tissue slices isolated from normal brain. This provides a framework for considering mechanisms that underlie the enduring predisposition of a brain to exhibit a seizure in the absence of an overt extrinsic stimulus. Finally, I present ways
629 citations
Cites methods from "Potassium accumulation in interstit..."
...This hypothesis is an extension of earlier ideas advanced by Green (1964) Fertziger and Ranck (1970) Dichter et al. (1972), Yaari et al. (1986) and others....
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TL;DR: There has been a new surge of interest in the functional significance of potassium distribution in the nervous system and the recent development of potassium-selective microelectrodes is supplemented by consulting more general reviews on brain electrolytes.
Abstract: Potassium, calcium, and magnesium are three inorganic ions that occur in significant quantity in extracellular fluid of the mammalian brain and have powerful effects on the functioning of nervous tissue. In different ways all three influence the excitability of neurons and the release of transmitters from presynaptic terminals. Two different points of view have evolved concerning the regulation of these ions in the central nervous system (CNS). Some authors have emphasized the narrow range of the activity of these ions in the healthy brain and have concluded that stability of brain function requires stability of the extracellular activity of these ions. Others have argued that in the course of evolution the mammalian brain must have found an advantageous use for these powerful agents in the normal regula tion of neuronal excitability. According to this view, programmed varia tions in [K+]o, [Ca2+]o, and perhaps also [Mg2+]o may be an integral component in the normal function of the central nervous system. Due to the recent development of potassium-selective microelectrodes (184) there has been a new surge of interest in the functional significance of potassium distribution in the nervous system. This selective review may be supplemented by consulting more general reviews on brain electrolytes (69, 72, 74, 83, 90, 158, 175).
444 citations
TL;DR: The hypothesis that penicillin, the most commonly used epileptogenic agent, brings about the following effects is outlined: a decrease in the threshold for impulse initiation in neurons within these pathways and/or by an increase in the potency of excitatory synaptic actions.
427 citations
TL;DR: The spread of epileptic activity throughout the brain, the development of primary generalized epilepsy, the existence of "gating" mechanisms in specific anatomic locations, and the extrapolation of hypotheses derived from simple models of focal epilepsy to explain more complex forms of human epilepsy are not yet fully understood.
Abstract: The cellular phenomena underlying focal epilepsy are currently understood in the context of contemporary concepts of cellular and synaptic function. Interictal discharges appear to be due to a combination of synaptic events and intrinsic currents, the exact proportion of which in any given neuron may vary according to the anatomic and functional substrate involved in the epileptic discharge and the epileptogenic agent used in a given model. The transition to seizure appears to be due to simultaneous increments in excitatory influences and decrements in inhibitory processes--both related to frequency-dependent neuronal events. A variety of specific hypotheses have been proposed to account for the increased excitability that occurs during epileptiform activity. Although each of the proposed mechanisms is likely to contribute significantly to the epileptic process, no single hypothesis provides an exclusive unifying framework within which all kinds of focal epilepsy can be understood. The spread of epileptic activity throughout the brain, the development of primary generalized epilepsy, the existence of "gating" mechanisms in specific anatomic locations, and the extrapolation of hypotheses derived from simple models of focal epilepsy to explain more complex forms of human epilepsy, all are not yet fully understood.
408 citations
References
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TL;DR: In the central nervous system of the leech, which contains smooth muscle cells in its connective tissue capsule, the effect of massive neuronal activity on the resting potential of glial cells could not be studied adequately because the preparation under these conditions dislodged the electrode.
Abstract: NEURONS AND G .LIAL CELLS in most parts of the nervo us system are intimately apposed, separated from each other by channels about 150 A. wide. It is natural to wonder whether the two types of cell influence one another either “electrically” (i.e., by current flow from one cell to the other) or by the release of a substance. It has been shown in the leech nervous system that if current is supplied to the interior of a nerve cell through an intracellular electrode, very little will enter the neighboring glial cell; most will pass through the intercellular clefts which have a relatively low resistance. Similarly, currents which flow during nerve impulses alter the membrane potential of the surrounding glia to a negligible extent good agreement with subsequent findings that the (10) clefts These results were in l between neurons and glial cells served as channels for the rapid diffusion of ions and of small molecules both in the leech and in amphibia (l&9). In the central nervous system of the leech, which contains smooth muscle cells in its connective tissue capsule, the effect of massive neuronal activity on the resting potential of glial cells could not be studied adequately because the preparation under these conditions and dislodged the electrode (1 0) . moved
1,188 citations
TL;DR: An intracellular analysis from the involved elements was carried out during the development and course of the organized rhythmical electrographic seizures simultaneously monitored with surface electrodes, finding that some neurons appear to be activated only in the later phases of the seizure.
767 citations
TL;DR: Reducing the concentrations of calcium and magnesium made the giant axon of Loligo spontaneously active and formed long trains of impulses in response to a single shock.
Abstract: The giant nerve fibres of Loligo and Sepia differ from most excitable tissues in that the spike of an isolated axon is followed by a brief period of hyperpolarization, which is often called the positive phase (Curtis & Cole, 1942; Hodgkin & Huxley, 1939; Weidmann, 1951). There is evidence that the positive phase occurs because the permeability of the membrane to potassium increases during the second half of the spike, and does not at once return to its resting value (Hodgkin & Huxley, 1952d). Since the resting potential of an isolated axon may be 15-30 mV less than the equilibrium potential for potassium ions, the persistence of the state of increased potassium permeability during the refractory period raises the membrane potential above its resting value and generates a pQsitive phase. This suggestion is supported by the observation that the membrane potential during the positive phase is markedly affected by small changes in the concentration of potassium outside the fibre (Hodgkin & Katz, 1949a, Hodgkin & Keynes, 1955). Thus, increasing the external potassium concentration from 0 to 20 mm, which decreases the resting potential by only about 10 mV, reduces the membrane potential during the positive phase by 30 mV. The sensitivity of the positive phase to changes in potassium concentration forms the basis for interpreting the observations described in this paper; the starting-point was provided by an experiment in which the effects of calciumdeficient solutions were being examined. Like many previous observers we found that reducing the concentrations of calcium and magnesium made the giant axon of Loligo spontaneously active. When fibres were near the point at which they fired continuously they often gave long trains of impulses in response to a single shock. In these trains we noticed that the positive phases of the spikes were not of equal size, but declined during the initial stages of the
697 citations
TL;DR: Possible mechanisms relating EEG waves to cellular potentials are discussed within the framework of transcortical and soma-apical dendrite potential distributions during different phases of physiological and pathological cortical activity.
291 citations
218 citations