[Extracellular Ca2+ and epilepsy. Examinations during normal and ictal activity in the somatosensory cortex of the cat].
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Animals↗
Biomedical subjects
U Heinemann
Publications and source records attributed to U Heinemann.
Stimulation induced changes in extracellular free calcium in normal cortex and chronic alumina cream foci of cats.
Changes in extracellular [Ca2+]0 (delta Ca) were measured with ion selective microelectrodes in the sensorimotor cortex of cats, surrounding alumina cream lesions and in the contralateral homotopic cortex. The lesions were produced by topical application of alumina cream 6 months-6 years prior to experiments. In normal cortex, stimulus induced reactions of [Ca2+]0 were found to be maximal (up to 0.45 mM) in depths of 200-300 micrometers below the cortical surface. At depths of 600 micrometers and more below the cortical surface, [Ca+2]0 usually rose by up to 0.2 mM above baseline. In the vicinity of the chronic lesion as well as in contralateral cortex [Ca2+]0 fell initially during stimulation in all depths. Close to the lesion delta Ca was as high as 0.8 mM and sites of maximal delta Ca were found to be located deeper in the cortex. About 5 mm from the scar as well as in the contralateral homotopic cortex, maximum delta Ca levels were found in a depth of 200-300 micrometers. It is suggested that Ca2+ dependent mechanisms are involved in epileptogenesis in chronic epileptic foci.
Aluminum↗
Effects of tetrodotoxin on changes in extracellular free calcium induced by repetitive electrical stimulation and iontophoretic application of excitatory amino acids in the sensorimotor cortex of cats.
Extracellular free calcium ([Ca2+]o) was measured with double barreled ion-sensitive reference electrodes in the sensorimotor cortex of cats before and after application of tetrodotoxin (TTX). Electrical stimulation of the cortical surface or of the thalamic ventrobasal complex resulted in reductions of [Ca2+]o (delta Ca) by up to 0.45 mM (baseline 1.2--1.3 mM). Iontophoretic applications of the excitatory amino acids glutamate, aspartate and DL-homocysteate evoked delta Ca by up to 1.2 mM. delta Ca were largest at a depth of 100-300 micron below cortical surface. After application of 10(-5) M TTX to the cortical surface, the delta Ca evoked by electrical stimulation disappeared and the accompanying slow negative potentials were reduced in amplitude. In contrast, delta Ca evoked by excitatory amino acids were only slightly affected. It is suggested that excitatory amino acids activate voltage-dependent postsynaptic Ca2+ conductances in neocortical neurones.
Amino Acids↗
[Mode of action of pentetrazole at the cellular level (author's transl)].
The question of the origin of the paroxysmal depolarization shifts which can be recorded from neurones within an experimental epileptogenic focus is still controversial. In this paper, a special reference is made to data obtained in thin hippocampal slices in vitro during intra- and extracellular recordings from CA1 pyramidal cell somas before and after pentylenetetrazole (PTZ) application onto the slice surface. It is shown that PTZ can decrease inhibitory potentials, increase membrane input resistance and increase action potential duration. Using calcium-selective microelectrodes, it is shown that PTZ can enhance the lowering of calcium ion concentration in extracellular space, which is normally induced by repetitive stimulations. These data, as well as those from others, support the hypothesis that paroxysmal depolarization shifts seen in hippocampus could result from the facilitation of a slow depolarizing calcium current through the cell membrane uncovered by a depression of repolarizing potassium current produced by the convulsants. The observed depression of inhibitory potential would further facilitate the development of long-lasting depolarizing potentials.
Action Potentials↗
Extracellular calcium and potassium changes in mammalian neocortex.
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Amino Acids↗
[Diminution of the extracellular concentration of calcium ions during focal epileptic crisis induced by enanthotoxin in the cat cortex].
OEnanthotoxin applied locally onto the Cat cortex produced a long-lasting epileptic focus. The basic cortical level of extracellular calcium concentration ([Ca2+]e) was decreased before the actual onset of paroxysmal discharges. In the active focus the [Ca2+]e decrease induced by a cortical or a thalamic stimulation was larger than in normal cortex. Maximal decreases were found at a depth of 300 micrometer below cortical surface. It is suggested that at this cortical level calcium conductances are increased by oenanthotoxin. This increase may be one of the mechanisms of onset of epileptic seizures.
Alkynes↗
Transient changes in the size of the extracellular space in the sensorimotor cortex of cats in relation to stimulus-induced changes in potassium concentration.
The time course of local changes of the extracellular space (ES) was investigated by measuring concentration changes of repeatedly injected tetramethylammonium (TMA+) and choline (Ch+) ions for which cell membranes are largely impermeable. After stimulus-induced extracellular [K+] elevations the delta [TMA+] and delta [Ch+] signals recorded with nominally K+-selective liquid ion-exchanger microelectrodes increased by up to 100%, thus indicating a reduction of the ES down to one half of its initial size. The shrinkage was maximal at sites where the K+ release into the ES was also largest. At very superficial and deep layers, however, considerable increases in extracellular K+ concentration were not accompanied by significant reductions in the ES. These findings can be explained as a consequence of K+ movement through spatially extended cell structures. Calculations based on a model combining the spatial buffer mechanism of Kuffler and Nicholls (1966) to osmolarity changes caused by selective K+ transport through primarily K+ permeable membranes support this concept. Following stimulation additional iontophoretically induced [K+]0 rises were reduced in amplitude by up to 35%, even at sites where maximal decreases of the ES were observed. This emphasizes the importance of active uptake for K+ clearance out of the ES.
Animals↗
Extracellular calcium activity changes in cat sensorimotor cortex induced by iontophoretic application of aminoacids.
Extracellular Ca2+ activity (aCa) changes were measured with Ca2+-sensitive microelectrodes in the cat cerebral cortex during iontophoretic administration of excitatory and inhibitory aminoacids. Glutamate, aspartate and DL homcysteate usually decreased aCa from a baseline of 1.3 mM to as low as 0.1 mM. The amplitude of the changes was largest at depths between 100 and 300 micrometer beneath the cortical surface. The aCa decreases could be deminished or blocked by Co2+, Mn2+ or La3+ as well as by GABA. These data suggest that large Ca2+ conductances that may be voltage-sensitive are present in apical dendrites of neocortical neurones.
Amino Acids↗
Crystallization of a complex between ribonuclease T1 and 2'-guanylic acid.
Ribonuclease T1 was crystallized under various conditions. Form I crystals were produced by microdialysis against 53% (v/v) 2-methyl-2,4-pentanediol in 0.01 M sodium acetate, 0.05% 2'-guanylic acid (2'GMP) and 0.02% NaN3 (pH 6.2-7.2). These crystals are tetragonal, space group P41212 and contain two molecules per asymmetric unit; cell dimensions are a = b = 5.86 nm, c = 13.28 nm. Form IIa and form IIb crystals were obtained by microdialysis from a buffer of 0.01-0.05 M sodium acetate, 0.25-0.5% 2'GMP, 0.02% NaN3 and 2-5 mM calcium acetate (pH 4.0-4.4) in the presence of 50-75% (v/v) 2-methyl-2,4-pentanediol. These crystals are orthorhombic, space group P212121, and contain one molecule per asymmetric unit; cell dimensions are a = 4.66 nm, b = 5.02 nm, c = 4.04 nm (form I) and alpha = 4.44 nm, b = 5.00 nm, c = 4.03 nm (form II). Using high-performance liquid chromatography, it could be shown for all crystal forms that 2'-GMP is bound in the crystals. The molecular ratio between RNase T1 and 2'GMP was 0.9 for form II crystals and thus agreed with a 1:1 enzyme-nucleotide complex. Heavy-atom derivatives were produced with lead acetate for form IIa crystals and with uranyl acetate for from IIb crystals. Three-dimensional X-ray analysis of the RNase-T1 x 2'GMP complex is under way.
Aspergillus oryzae↗
[Calcium, potassium and chloride: studies on experimental epilepsy].
Convulsive manifestations are synchronized mass-discharges which are caused by a dysfunction of the dynamic equilibrium between excitation and inhibition. This is caused by a change in membrane activity which increases or decreases the effectiveness of neurotransmitters. We showed the effect of ions on membrane activity and epileptic discharges.
Calcium↗
Stimulus induced and seizure related changes in extracellular potassium concentration in cat thalamus (VPL).
Extracellular potassium activity (ak) and field potentials (fp) were measured in the nucleus ventro-postero-lateralis (VPL) thalami in order to assess the extent of thalamic participation in cortical seizure activity. Small increases (up to 0.7 mmole/l) or decreases (up to 0.2 mmole/l) in ak were induced by electrical stimulation of the contralateral forepaw. These changes in ak were spatially more limited than the simultaneously recorded fp. Similar observations were made during weak electrical stimulation of the somatosensory cortex and during interictal spikes in a cortical penicillin focus. Large and widespread increases in ak to levels of 11.6 mmoles/l and slow negative fps of 8 mV accompanied seizure generation either in a cortical penicillin focus or during intense repetitive electrical stimulation of the cortical surface. Subsequent to such increases ak fell to subnormal levels. The amplitudes and durations of such undershoots were correlated with the amplitudes of the preceding increases in ak. Sometimes thalamic seizures ceases before cortical epileptic episodes. This resulted in a decrease of cortical EEG amplitudes. After ablation of the sensorimotor cortex seizures in forepaw-VPL could be induced by stimulation of the somatosensory cortex. These results further support the conclusion that specific thalamic nuclei participate in seizure generation and may serve as a subcortical route of seizure spread.
Afferent Pathways↗
Relation between extracellular potassium concentration and neuronal activities in cat thalamus (VPL) during projection of cortical epileptiform discharge.
Neuronal and potassium activities (ak) were measured in the nucleus ventro-posterolateralis thalami (VPL) during propagated epileptiform activity from the somatosensory cortex of cats. Seizures were induced by repetitive electrical stimulation of the cortical surface or by topical application of penicillin. The recruitment of VPL into a seizure resulted in large increases of ak to levels of up to 11.6 mmoles/l, accompanied by increased in neuronal discharge rate to 300/sec. Sometimes the rise in ak preceded active participation of a given thalamo-cortical relay (TCR) neuron in the seizure. After reaching a peak level, ak and neuronal discharge rate slowly declined during an ictal episode. After cessation of seizures all TCR neurons were inhibited, while ak fell to subnormal levels. The duration of these postictal depressions increased with the amplitude of preceding increases and subsequent undershoots in ak and could last up to 120 sec. During decay and undershoot in ak, relay capability of TCR neurons was reduced. Also the probability that action potentials elicited in intracortical endings of TCR cells would antidromically invade their cell bodies was decreased. The duration of these periods varied with the amplitude of undershoot in ak. Seizure threshold was increased during undershoots. These observations are consistent with a long-lasting postictal hyperpolarization of neuronal membranes. The hyperpolarization may be caused by the action of an electrogenic pump, which is probably involved in termination of seizure discharge.
Animals↗
Ionic changes during experimentally induced seizure activity.
Changes in intra- and extracellular ionic activity and their relation to generation and termination of seizure phenomena can be studied with the help of ion-selective microelectrodes. Transient changes in extracellular potassium activity (aK) of the cortex regularly accompany paroxysmal activity induced by electrical stimulation and pentylenetetrazol injections or occur within active penicillin and aluminum foci. A rise of aK from baseline levels of about 3 mmoles/l up to ceiling levels of 8--12 mmoles/l, followed by subnormal K activity, is typically found during seizure discharge. Extracellular K accumulation during seizures facilitates the spread into extrafocal regions. Ceiling levels of extracellular aK are characterized by pronounced K reabsorption which is probably a limiting mechanism for the rise in extracellular aK. It may be a consequence of a simultaneous rise in intracellular Na activity that an electrogenic Na--K exchange process is involved in the termination of ictal activity. Seizures are also accompanied by significant reductions in extracellular Ca2+ activity (aCa) to as low as 0.7 mmoles/l (resting aCa 1.25 mmoles/l). There is no critical level of lowered aCa at which a seizure ultimately results. However, unlike changes in aK reductions in aCa can precede ictal activity. Thus, a fall of aCa occurs before the onset of paroxysmal periods during cyclical spike driving in a penicillin focus and before seizures induced by pentylenetetrazol. Ca2+-dependent mechanisms may contribute to seizure generation. In addition to changes in aK and aCa, intracellular chloride activity (aCl) can increase during seizure activity, as a result of an impaired chloride extrusion mechanism, which would lead to a reduced efficacy of inhibitory synaptic transmission and, therefore, to facilitation of seizure generation.
Animals↗
Extracellular free calcium and potassium during paroxsmal activity in the cerebral cortex of the cat.
Extracellular calcium and potassium activities (aCa and aK) as well as neuronal activity were simultaneously recorded with ion-sensitive electrodes in the somatosensory cortex of cats. Baseline aCa was 1.2-1.5 mM/l, baseline aK 2.7-3.2 mM/l. Transient decreases in aCa and simultaneous increases in aK were evoked by repetitive stimulation of the contralateral forepaw, the nucleus ventroposterolateralis thalami and the cortical surface. Considerable decreases in aCa (by up to 0.7 mM/l) were found during seizure activity. A fall in aCa preceded the onset of paroxysmal discharges and the rise in aK after injection of pentylene tetrazol. The decrease in aCa led also the rise in aK during cyclical spike driving in a penicillin focus. It is concluded that alterations of Ca++ dependent mechanisms participate in the generation of epileptic activity.
Animals↗
Ceiling of stimulus induced rises in extracellular potassium concentration in the cerebral cortex of cat.
Levels of extracellular potassium activity (aK) during repetitive electrical stimulation were measured with ion sensitive microelectrodes in the somatosensory cortex of the cat to determine maximum values ("ceiling" levels) under different experimental conditions. The maximal values of aK were 10.2 mequiv./1 during stimulation of the cortical surface (CS) or of the nucleus ventroposterolateralis thalami (VPL) and during selfsustained afterdischarges (SAD). Similarly, peak values were 6.5 mequiv./1 for the nucleus ventrolateralis anterior and 4 mequiv./1 for the nucleus centromedianus as well as for the nucleus cuneatus. The rise in aK during a test stimulus with constant intensity and frequency was inversely related to the level of aK produced by a preceding stimulation. Also rise in aK during SAD was smaller when it started from an enhanced level of aK. During repetitive stimulation of CS or VPL a rise in aK was not observed when aK was increased to levels above 10 mequiv./1 by superfusion with potassium enriched solutions. An electrophoretically evoked K+ test signal was reduced between 10 and 48% when applied during stimulus induced increased levels of aK. Stimulus induced potassium changes could become negative when aK was increased to levels above 7 mequiv./1 by local electrophoresis, while the stimulus induced increase in neuronal discharge rate did not disappear or reverse. Amplitudes of ECoG and local evoked potentials were reduced as aK increased during stimulation or superfusion. It is suggested that the ceiling in its steady state is maintained by an active K+ uptake mechanism which balances extra releases of K+. Decreased release of K+ at increased levels of aK may in addition limit the rise in aK.
Animals↗
Relationship between background activity and subclinical seizure pattern.
Open- and closed-eyed EEG records were made in frontal, temporal and occipital regions, in order to examine the time relationships between various of their characteristics, in connection with the appearance of subclinical seizure patterns. 1. In the range of alpha frequency, both with open and closed eyes, the standard deviation of frequency over all brain areas decreased both before and after subclinical seizure patterns as compared to periods without pattern, and the number of temporal waves was reduced. Frontally, the mean amplitude was increased only in open-eyed records. The time relationship of the appearance of alpha maxima differed over all regions, but was closest in frontal records in both open- and closed-eyed records, and independent of the pathological pattern. In closed-eyed frontal records, a changeover in the time lead between the hemispheres could be observed, with one side leading during the period preceding the pattern, and the other after the pattern. 2. In the range of theta frequency, occipital open-eyed records showed slowing of the frequency both before and after the subclinical seizure pattern, with an increase in the standard deviation. In closed-eyed records made in the period preceding the pattern, an increase of the mean amplitude was observed frontally and occipitally, as well as an increase of the standard deviation of the amplitude in all regions. Slowing of the theta frequency was encountered in the frontal regions. Differences in the periods preceding and following subclinical seizures were to be seen only in the theta range.
Adult↗
Undershoots following stimulus-induced rises of extracellular potassium concentration in cerebral cortex of cat.
Extracellular potassium activity (ak) was recorded with potassium-sensitive electrodes in the sensorimotor cortex of cats. Resting activity was 2.8--3.4 mEquiv/l. Electric stimulation of the cortical surface and the nucleus ventroposterolateralis of the thalamus brought about an increase in aK followed by an undershoot and return to normal value. The lowest observed value of aK was 2.1 mEquiv./l. Size and duration (range 0.5--4 min) of the undershoots of aK increased with increasing peak amplitudes of the preceding rise in aK. Following the rise in aK, a period of reduced neuronal activity was observed which usually shorter lasting than the decrease in extracellular aK. An undershoot of aK and a concomitant reduction of neuronal discharge frequency can also occur in immediate response to antidromic stimulation of the pyramidal tract. To compare the K+ redistribution at normal and reduced levels of aK electrophoretic K+ signals were produced with constant current pulses from a proximate KCl-filled capillary. Both amplitudes and half times of decay of these K+ signals were found to decrease during the phase of poststimulatory undershoot in aK (19 and 23% respectively). It is suggested that an activated reuptake of potassium contributes to the decrease in extracellular aK in addition to inhibitory processes.
Animals↗
Inter-hemispheric "synchrony" of alpha waves.
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Adult↗