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Biomedical subjects

U Heinemann

Publications and source records attributed to U Heinemann.

At least 325 records · Page 18Linked to original sources
PubMed1987

Pre- and postsynaptic K+ and Ca2+ fluxes in area CA1 of the rat hippocampus in vitro: effects of Ni2+, TEA and 4-AP.

Pre- and postsynaptic fluxes of Ca2+ and K+ were determined concurrently in CA1 of the hippocampus in vitro under conditions where synaptic transmission was blocked. The Ca2+ entry blocker, Ni2+, abolished both pre- and postsynaptic Ca2+-influx and reduced presynaptic K+-efflux by about 20%. Postsynaptic K+-efflux was reduced nearly by 60%. 4-aminopyridine (4-AP) strongly enhanced presynaptic Ca2+-influx but only marginally increased Ca2+-entry into the postsynaptic neurones. At the same time, total K+-efflux from presynaptic sites was increased by about 30% but was unaltered postsynaptically. Finally, tetraethylammonium (TEA) enhanced both pre- and postsynaptic Ca2+-influx. Postsynaptic influx was more profoundly affected than presynaptic. Neither pre- nor postsynaptic efflux of K+ was altered by TEA. The results indicate a complex balance between inward Ca2+ and outward K+ currents in CA1 and that this balance may differ pre- and postsynaptically.

4-Aminopyridine↗
PubMed1987

Epileptiform activity induced by lowering extracellular [Mg2+] in combined hippocampal-entorhinal cortex slices: modulation by receptors for norepinephrine and N-methyl-D-aspartate.

Reduction of extracellular Mg2+ concentration induced spontaneous and evoked epileptiform activity in the entorhinal cortex (EC) and dentate gyrus (DG) of combined hippocampus (HC)-EC slices. Extracellular field potentials, as well as changes in extracellular Ca2+ and K+ concentrations, were measured in EC and DG with ion-selective/reference electrodes during both repetitive and single stimuli. In the EC, lowering extracellular [Mg2+] induces both spontaneous and single stimulus evoked ictal events consisting of extracellular negative potential shifts (up to 5 mV, 30 sec), decreases in [Ca2+]0 and increases in [K+]0. In the DG, spontaneous events were much shorter, but similar changes in [Ca2+]0, [K+]0 and field potentials (FPs) could be evoked by brief high-frequency stimulation. In both areas, the N-methyl-D-aspartate (NMDA) receptor antagonist 2-aminophosphonovalerate (2-APV) completely blocked spontaneous as well as stimulus evoked epileptiform events. The neurotransmitter norepinephrine (NE), which has previously been shown to modulate long-term potentiation in the DG, was found to exhibit differential modulation of epileptiform activity in the EC and DG. In the EC, NE, acting via alpha 1-receptors, completely blocked low Mg2+-induced epileptiform activity. In contrast, in the DG, NE exhibited a beta-receptor mediated prolongation of the low Mg2+-induced ictal events, and enhanced the stimulus-induced ionic and field potential changes. From these results, we conclude that lowering extracellular [Mg2+], acting in large part through the removal of the Mg2+ voltage-dependent blockade of NMDA receptors, leads to induction of epileptiform activity in both the EC and DG.(ABSTRACT TRUNCATED AT 250 WORDS)

2-Amino-5-phosphonovalerate↗
PubMed1987

Low extracellular magnesium induces epileptiform activity and spreading depression in rat hippocampal slices.

The effect of low extracellular Mg2+ concentration ([Mg2+]o) on neuronal activity was studied in rat hippocampal slices. After 20-40 min of perfusion with Mg2+-free medium, when [Mg2+]o declined to approximately 0.1-0.4 mM, spontaneous field potentials developed in the CA1 and CA3 regions, but not in the dentate gyrus. In the CA3 pyramidal cell layer, these potentials consisted of repetitive (0.3-0.5 Hz), 40- to 120-ms-long positive deflections (2-5 mV) with superimposed population spikes. In the stratum (str.) pyramidale of the CA1 region, positive-negative deflections (less than 3 mV) lasting for 30-80 ms were observed, which occurred with a frequency of 0.3-0.5 Hz. In some cases, longer lasting and rapidly recurring events were also observed. In CA3 pyramidal cells, the intracellular correlates of the field potential transients were 20- to 30-mV paroxysmal depolarization shifts (PDS) with superimposed bursts of action potentials, followed by large (greater than 10 mV), 500- to 1,200-ms-long afterhyperpolarizations (AHP). In contrast, pyramidal neurons of the CA1 area did not show PDSs; instead, sequences of excitatory postsynaptic potentials (EPSPs)/inhibitory postsynaptic potentials (IPSPs) accompanied the transient field potential changes. Occasionally, spontaneous EPSPs/IPSPs, occurring with high frequencies, could also be observed in CA1 without any field potential transients. In both hippocampal regions, the epileptiform activity evolved without significant alterations in the resting membrane potential (RMP) and input resistance (RN) of the neurons, although a 2- to 5-mV reduction in action potential threshold was noted. The spontaneous activity in Mg2+-free medium was readily suppressed by raising the extracellular Ca2+ concentration ([Ca2+]o) from 1.6 to 3.6 mM. The perfusion of 10-30 microns DL-2-amino-5-phosphonovaleric acid (2-APV), an antagonist for the glutamate receptors of the N-methyl-D-aspartate (NMDA) type, also attenuated or reversibly blocked the spontaneous activity. Surgical isolation of area CA1 from CA3 ceased the occurrence of the transients in CA1 but not in CA3. The synaptic input/output curves were shifted to the left in the absence of [Mg2+]o. Threshold intensity for eliciting population spikes was 50-75% of that in normal medium. Paired-pulse facilitation was still present near threshold, but was reduced at higher stimulus intensities. Decreases in [Ca2+]o, produced by repetitive stimulation (20-Hz/5-10 s) of the Schaffer collateral/commissural pathway and monitored with ion-selective microelectrodes in the CA1 region, were enhanced in Mg2+-free medium.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1986

The action of valproate on spontaneous epileptiform activity in the absence of synaptic transmission and on evoked changes in [Ca2+]o and [K+]o in the hippocampal slice.

The effects of valproate (VPA) on neuronal excitability and on changes in extracellular potassium ([K+]o) and calcium ([Ca2+]o) were investigated with ion selective-reference electrode pairs in area CA1 of rat hippocampal slices. Field potential responses to single ortho- and antidromic stimuli were unaltered by VPA (1-5 mM). The afferent volley evoked in the Schaffer-commissural fibers was also unaffected. In contrast, VPA (1 mM) depressed frequency potentiation and paired pulse facilitation markedly. Decreases in [Ca2+]o induced either by repetitive stimulation or by application of the excitatory amino acids N-methyl-D-aspartate and quisqualate were reduced, and the latter results suggest that VPA interferes with postsynaptic Ca2+ entry. When synaptic transmission was blocked by lowering [Ca2+]o (0.2 mM) and elevating [Mg2+]o (7 mM), prolonged afterdischarges elicited by antidromic stimulation were blocked by VPA. VPA also suppressed the spontaneous epileptiform activity seen when [Ca2+]o was lowered to 0.2 mM, without elevating [Mg2+]o. The amplitudes of the rises in [K+]o induced by repetitive orthodromic stimulation were only slightly depressed and those elicited by antidromic stimulation were generally unaltered by VPA, as were laminar profiles of stimulus-evoked [K+]o signals. These results indicate that VPA has membrane actions in addition to known effects on excitatory and inhibitory transmitter pools.

Animals↗
PubMed1986

An N-methyl-D-aspartate (NMDA) receptor antagonist reduces bicuculline-induced depolarization shifts in neocortical explant cultures.

We investigated the actions of a specific N-methyl-D-aspartate (NMDA) antagonist, 2-amino-5-phosphonovaleric acid (2-APV), on bicuculline-induced epileptogenesis in organotypic explant cultures from neonatal rat neocortex. Explants were maintained in roller tubes for 3-5 weeks. The late, plateau phase of the intracellularly recorded paroxysmal depolarization shift was sensitive to both intracellularly injected hyperpolarizing currents and 2-APV, suggesting that this component is generated by a voltage-dependent, regenerative process that is mediated by activation of NMDA receptors. The results support the hypothesis that NMDA receptors play an important role in the generation of epileptiform activity by localized circuits of neocortical neurons.

2-Amino-5-phosphonovalerate↗
PubMed1986

Laminar profiles of the changes in extracellular calcium concentration induced by repetitive stimulation and excitatory amino acids in the rat dentate gyrus.

Changes in extracellular free calcium concentration ([Ca2+]o) were measured with ion-selective microelectrodes in the dentate gyrus of the rat hippocampal slice preparation. Repetitive stimulation (20 Hz/10 s) of the perforant path or mossy fibers, or alternatively, iontophoresis of the excitatory amino acids N-methyl-D-aspartate (NMDA) or quisqualate (Quis) elicited decreases in [Ca2+]o (delta Ca2+) which were unequally distributed along the axis of the granule cells. Laminar profiles of the [Ca2+]o changes revealed marked differences between stimulus- and amino acid-induced responses. The delta Ca2+ induced by either anti- or orthodromic stimulation were relatively small (less than 0.15 mM) and were found to be maximal at the cell body layer (stratum granulosum). In contrast, the excitatory amino acids NMDA and Quis evoked large delta Ca2+ (greater than 1.2 mM) which were maximal at dendritic sites, 100 microns away from the cell body layer in the inner stratum moleculare. The effect of NMDA was reversibly blocked by 2-amino-5-phosphonovaleric acid without antagonism of the synaptic responses or the stimulus-induced changes in [Ca2+]o. Therefore, under normal conditions, NMDA receptors appear not to participate in synaptically induced delta Ca2+ in the dentate gyrus.

Amino Acids↗
PubMed1986

Epileptiform activity in combined slices of the hippocampus, subiculum and entorhinal cortex during perfusion with low magnesium medium.

Reduction of [Mg2+]o induced spontaneous epileptiform activity consisting of 40-100-ms bursts of population spikes in hippocampal slices. This activity disappeared from area CA1 when the connections to area CA3 were cut, but persisted in isolated minislices of area CA3. Spontaneous activity was also observed in the dentate gyrus, provided that the connections to the subiculum and entorhinal cortex (EC) were intact. In the parasubiculum and EC longer lasting epileptiform events were observed which resembled seizure-like behaviour. The epileptiform activity was completely suppressed by 2-aminophosphonovalerate (30 microM) suggesting that N-methyl-D-aspartate receptors for excitatory amino acid transmitters participate in the generation of this activity. These findings show that the EC possesses properties which permit the generation of seizure-like activity in contrast to the hippocampus where the activity resembled recurrent interictal events.

Action Potentials↗
PubMed1986

Norepinephrine enhances stimulus-evoked calcium and potassium concentration changes in dentate granule cell layer.

Changes in extracellular Ca2+ and K+ concentrations were measured in the dentate gyrus with ion-selective/reference electrodes during high-frequency perforant path stimulation. Bath application of norepinephrine (NE, 50 microM) markedly enhanced both evoked decreases in extracellular calcium and increases in extracellular potassium concentration. These effects of NE were observed in the granule cell layer (stratum granulosum), but not 200 microns away in the dendritic layer (stratum moleculare). The beta-antagonist propranolol (1 microM) completely blocked the NE-induced enhancement of Ca2+ signals in the dentate. In contrast to the dentate, NE did not enhance evoked Ca2+ of K+ concentration changes in the CA1 pyramidal cell layer. These results indicate that NE markedly enhanced both Ca2+ and K+ fluxes, probably by a beta-receptor-mediated mechanism, in the dentate gyrus during high-frequency stimulation of a type able to elicit long-term potentiation (LTP). These increases may underly the action of NE in modulating LTP in the dentate gyrus.

Animals↗
PubMed1986

Differential effect of adenosine on pre- and postsynaptic calcium fluxes.

In rat hippocampal slices, stimulus-evoked field potentials and the concomitant decrease of the extracellular concentration of free Ca ions [Ca2+]o were measured with combined reference/ion-sensitive microelectrodes. By reducing [Ca2+]o from 2.0 mM to 0.2 mM, evoked synaptic transmission was blocked, but orthodromic repetitive stimulation of CA1 afferents still elicited a marked decrease of [Ca2+]o. This Ca2+ signal is attributed predominantly to Ca2+ entry into the activated axon terminals. It was significantly depressed by adenosine. The adenosine agonist, L-phenylisopropyl adenosine (L-PIA) was more effective than D-PIA, indicating that the adenosine depression of presynaptic Ca2+ entry is mediated via the A1 receptor. 4-Aminopyridine (4-AP) enhanced decreases in [Ca2+]o without restoring synaptic transmission. Adenosine depressed also these Ca2+ signals. Adenosine deaminase was even more effective in the presence of 4-AP and enhanced the orthodromic Ca2+-signal by a factor of two. Antidromic stimulation of hippocampal pyramidal cells also evoked reductions in [Ca2+]o. These were less affected by adenosine and the other treatments under the conditions tested.

Adenosine↗
PubMed1986

Excitatory amino acids and epilepsy-induced changes in extracellular space size.

Convulsant and stimulus induced seizures are associated with Ca, Na, K and Cl concentration changes in the extracellular space (ES), which are a resultant of transmembrane ionic fluxes and of changes in the ES size. The ES decreases on average by 30% during a single seizure. An analysis of the causes of ES size changes reveal a large contribution from the spatial glia K buffer mechanism which may account for up to 60% of the ES decreases. NaCl and KCl uptake into cells as well as increases in intracellular osmolarity due to anaerobic glycolysis contribute less to the local cytotoxic edema but account for a net gain of osmotic active particle at the site of the focus. Excitatory amino acids such as glutamate, aspartate, N-methyl-D-aspartate (NMDA), kainate and quisqualate also lead to Na, Cl and eventually Ca uptake into cells and to release of K with dose dependent decreases in [Na]o, [Ca]o and [Cl]o, increases in [K]o and transient decreases in ES size by up to 80% which are possibly associated with a net reduction of osmotically active particles. The predominant cause for this cytotoxic edema is NaCl uptake into cells but spatial K buffering through glial cells also contributes to this type of edema. The possible consequences of the various ion movements and the changes in osmolarity as well as ES size for tissue vulnerability are discussed.

Animals↗
PubMed1986

Effects of GABA and bicuculline on N-methyl-D-aspartate- and quisqualate-induced reductions in extracellular free calcium in area CA1 of the hippocampal slice.

Decreases in extracellular free calcium ([Ca2+]o) and concomitant field potentials were recorded from the dendritic and cell body layers of the CA1 field in transverse hippocampal slices. They were elicited by tetanic stimulation of Schaffer collaterals and commissural fibers or by iontophoretic application of the excitatory amino acids N-methyl-D-aspartate (NMDA) and quisqualate (Quis). Under control conditions, decreases in [Ca2+]o were found to be maximal in stratum pyramidale (SP). In stratum radiatum (SR), 100 micron away from SP, decreases in [Ca2+]o were half the size of those observed in SP. Bicuculline methiodide, bath-applied at concentrations of 10-100 microM, enhanced the reductions in [Ca2+]o, increased the field potentials in all layers and also induced "spontaneous" epileptiform activity. In the presence of bicuculline, the decreases in [Ca2+]o were particularly enhanced in SR and were often greater than those recorded in SP. This was the case for changes in [Ca2+]o induced either by repetitive electrical stimulation or by application of NMDA and Quis. When synaptic transmission was blocked by perfusing the slices with a low Ca2+ medium, all NMDA and Quis-induced changes in [Ca2+]o were predictably reduced but there was a relative enhancement of changes in [Ca2+]o in SR with respect to those in SP. We propose that, under normal conditions, an inhibitory control mediated by GABA limits the reductions of [Ca2+]o particularly in SR. In support of this proposal, we found that bath-applied GABA had a depressant action on changes in [Ca2+]o.

Animals↗
PubMed1986

Step reductions in extracellular Ca2+ activate a transient inward current in chick dorsal root ganglion cells.

We investigated whether transient step reductions in divalent cations would produce detectable changes in neuronal excitability similar to those reported in the total absence of divalent cations. Using cultured chick dorsal root ganglion cells as a model system, our results indicate that a step reduction in divalent cations induces a transient inward current. This response is mediated by a tetrodotoxin-resistant, Na+-permeable, cation channel that is blocked by cadmium. This, and our observation that the response is abolished by verapamil, suggests that the current passes through calcium channels. This transient inward current was estimated to be activated by decreases in extracellular calcium ([Ca2+]o) as small as 0.5-0.8 mM and thus represents a different response from the one previously observed when steady-state [Ca2+]o levels were reduced to micromolar levels.

Animals↗
PubMed1986

Dynamic variations of the brain cell microenvironment in relation to neuronal hyperactivity.

Neuronal hyperactivity has been shown to cause transient changes in ionic concentrations as well as in the volume of the extracellular space (ECS). During enhanced neuronal activity in the sensorimotor cortex of the cat, increases in the extracellular K+ concentration to a ceiling value of 10 mM have been observed concomitant with decreases in the Na+ concentration of similar magnitude. Simultaneously, the Cl- concentration rose steadily during the enhanced neuronal activity, and the extracellular space decreased by about 30%. A mathematical model allowed the interpretation of these concentration and volume changes as results of K+ release by active neurons in exchange for Na+, removal of K+ from the ECS by spatial glial buffering and movements of KCl into glial cells, as well as cell swelling due to metabolically induced transient increases in cellular osmolarity. Similar mechanisms have also been found to operate in gliotic scar tissue, where glial cells appeared to function the same way as in normal cortex, in rat hippocampal slices, and in preparations studied by other investigators.

Animals↗
PubMed1986

Nonsynaptic epileptogenesis in the mammalian hippocampus in vitro. I. Development of seizurelike activity in low extracellular calcium.

Epileptiform activity induced in rat hippocampal slices by lowering extracellular Ca2+ concentration ([Ca2+]o) was studied with extracellular and intracellular recordings. Perfusing the slices with low Ca2+ (less than or equal to 0.2 mM) or EGTA-containing solutions blocked the synaptic responses of hippocampal pyramidal cells (HPCs). Despite the block, spontaneous paroxysms, termed seizurelike events (SLEs), appeared in the CA1 area and then recurred regularly at a stable frequency. Transient hypoxia accelerated their development and increased their frequency. When [Ca2+]o was raised in a stepwise manner, the SLEs disappeared at 0.3 mM. With extracellular recording from the CA1 stratum pyramidale, a SLE was characterized by a large negative shift in the field potential, which lasted for several seconds. During this period a large population of CA1 neurons discharged intensely and often in synchrony, as concluded from the frequent appearance of population spikes. Synchronization, however, was not a necessary precursor for the development of paroxysmal activity, but seemed to be the end result of massive neuronal excitation. The cellular counterpart of a SLE, as revealed by intracellular recording from HPCs in the discharge zone of the paroxysms, was a long-lasting depolarization shift (LDS) of up to 20 mV. This was accompanied by accelerated firing of the neuron. A prolonged after-hyperpolarization succeeded each LDS and arrested cell firing. Brief (approximately 50 ms) bursts were commonly observed before LDS onset. Single electrical stimuli applied focally to the stratum pyramidale or alveus evoked paroxysms identical to the spontaneous SLEs, provided they surpassed a critical threshold intensity. Subthreshold stimuli elicited only small local responses, whereas stimuli of varied suprathreshold intensities evoked the same maximal SLEs. Thus the buildup of a SLE is an all or nothing or a regenerative process, which mobilizes the majority, if not all, of the local neuronal population. Each SLE was followed by absolute and relative refractory periods during which focal stimulation was, respectively, ineffective and less effective in evoking a maximal SLE. In most slices the spontaneous SLEs commenced at a "focus" located in the CA1a subarea (near the subiculum). SLEs evoked by focal stimulation arose near the stimulating electrode. From their site of origin the paroxysmal discharges spread transversely through the entire CA1 area at a mean velocity of 1.74 mm/s. Consequently, the discharge zone of a SLE could encompass for several seconds the entire CA1 area.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1986

Nonsynaptic epileptogenesis in the mammalian hippocampus in vitro. II. Role of extracellular potassium.

The role of extracellular K+ (K+o) in nonsynaptic epileptogenesis induced in the CA1 area of rat hippocampal slices by lowering [Ca2]o was studied with K+-selective microelectrodes (KSMs). Extracellular field potentials and [K+]o were recorded simultaneously with 1-2 KSMs in the CA1 stratum pyramidale. In slices perfused with an oxygenated standard physiological solution (containing 2 mM Ca2+), base-line [K+]o was stable for several hours. The washout of Ca2+o was accompanied by a gradual tonic rise of [K+]o. Spontaneous and stimulus-evoked maximal seizurelike events (SLEs) appeared when [K+]o was approximately 0.5 mM above the initial 5 mM base line. These changes were reversible in normal medium. When K+o was pressure ejected in the CA1 stratum pyramidale of spontaneously active slices, a local rise in [K+]o of approximately 0.5 mM was necessary to trigger a SLE. A similar apparent [K+]o "threshold" was associated with SLEs evoked by electrical stimulation. Increasing [K+] in the perfusing solution by small increments (1 mM) markedly enhanced SLEs frequency and velocity of spread and decreased the period of absolute refractoriness that succeeded each paroxysm. Similar changes occurred during periods of transient hypoxia. Small [K+] decreases in the perfusate had the converse effects. Spontaneous SLEs were associated with phasic increases in [K+]o. In simultaneous [K+]o recordings from two layers, these transients were largest (up to 3.5 mM above base line) and rose more steeply at the stratum pyramidale. Toward the outer dendritic layers they became smaller, slower in time course, and delayed in onset. We conclude that the main source for these [K+]o transients are the hippocampal pyramidal cell bodies, which discharge intensely during a SLE, and that excess K+o is spatially dispersed around the discharge zone of the paroxysm. [K+]o continued to rise, though at a slower rate, throughout the course of a SLE. Following SLE termination, [K+]o decayed slowly to base line. The invasion of a CA1 region by a propagating SLE was preceded quite often by a slow rise in [K+]o. A sudden transition to a steeply rising [K+]o marked the explosive recruitment of this region into the discharge zone of the spreading paroxysm. The total (tonic and phasic) increase in [K+]o during SLEs did not surpass a maximal level of approximately 9 mM, which was the ceiling level of [K+]o in low [Ca2+]o. However, when spreading depression occurred, [K+]o rose up to 30-40 mM for several minutes. Spreading depression rarely appeared spontaneously despite the recurrence of SLEs, but could be provoked by repetitive electrical stimulation.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1986

Ionic changes and alterations in the size of the extracellular space during epileptic activity.

Experiments with ion-selective microelectrodes revealed that a considerable activity of K ions appears temporarily in the extracellular space (ES) during enhanced neuronal activity and is removed from the ES by diffusion, active uptake, and entry into glial cells. The glial uptake results from the preferential glial K permeability and spatial glial K buffering. The glia responds to the local extracellular accumulation by a depolarization of the exposed part of its membrane. This depolarization will spread along the glial syncytium or extended glial cells. At sites where the extracellular K concentration has not yet increased, the membrane potential will thus be depolarized with respect to the K diffusion potential. Here K will move from the intra- into the extracellular space, in order to restore the electrochemical equilibrium. This induces a current that carries K into glial cells at sites of maximal K accumulation and that transports K out of glial cells at remote areas. In this way K is spatially redistributed. The corresponding current loop in the ES is predominantly carried by Na and Cl, the majority ions. Thus, Na and Ca are transported to the site of K accumulation while Cl moves away. The Cl and K ions are only partially replaced by Na. Hence, a decrease of extracellular osmolarity results, which leads to a water flux from the ES into the cells, inducing a shrinkage of the ES at sites of maximal K accumulation. At remote sites, the opposite effect is expected due to K flow out of glia and Cl transport to these sites. Thus, remote from the area of maximal neuronal activity, an increase of the ES is expected. This mechanism can explain the measured depth profile of the changes in the ES. At sites of maximal neuronal activity, the extracellular space undergoes a reduction by more than 30%. The ionic changes are accompanied by slow negative potential shifts. An increase in intracellular osmolarity due to enhanced metabolic activity and possibly KCl uptake mechanisms contributes to the changes in volume and ionic concentration. Model calculations of the after-effects of the loss of positive charges from the extracellular space and the K-specific glial buffering could predict size and time course of these changes. Experimental tests of this view include observations during epileptiform activity in gliotic scar foci as well as in hippocampal slices with depressed synaptic transmission. The extra- and intracellular ionic changes influence the generation, spread, and termination of seizure activity.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1986

Extracellular calcium and potassium concentration changes in chronic epileptic brain tissue.

Repetitive electrical stimulation and application of excitatory amino acids lead to decreases in extracellular Ca2+ concentration and to rises in extracellular K+ concentration [( Ca2+]o, [K+]o) with a typical laminar distribution in a given neo- or allocortical structure. These ionic changes result from transmembrane ion fluxes along their respective electrochemical gradients. Epileptogenic drugs that impair repolarizing K+ conductances or inhibitory synaptic transmission enhance such extracellular ionic changes, but they do not alter the laminar distribution of [K+]o and [Ca2+]o changes. Enhanced [Ca2+]o concentration changes are also observed in chronic epilepsies such as the chronic alumina cream and cobalt focus, the kindling epilepsy, and during photically induced seizures in the baboon Papio papio. In chronic epilepsies, the sites of maximal [Ca2+]o changes shift to other layers, suggesting changes in the distribution of ion channels over the surface of nerve cells that may be involved in epileptogenesis in chronic epilepsies. The K+ and Ca2+ concentration changes associated with seizure contribute to the generation and spread of epileptic activity. This is demonstrated by the fact that lowering of extracellular free calcium concentration can induce spreading epileptiform activity in the absence of chemical synaptic transmission, with [K+]o rises preceding epileptiform activity.

Aluminum Oxide↗