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H D Lux

Publications and source records attributed to H D Lux.

At least 19 recordsLinked to original sources
PubMed1992

Evans blue reduces macroscopic desensitization of non-NMDA receptor mediated currents and prolongs excitatory postsynaptic currents in cultured rat thalamic neurons.

Fast application of L-glutamate, AMPA (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) or kainate to cultured rat thalamic neurons revealed properties of non-NMDA (N-methyl-D-aspartate) receptors similar to those described in hippocampal neurons. The kinetics of non-NMDA receptor-mediated currents were altered by the addition of the dye Evans Blue (EB). Macroscopic desensitization was reduced and activation and deactivation kinetics were slowed. Delayed addition of EB, after desensitization of non-NMDA receptors, resulted in reactivation of desensitized receptors. Thus, both ion channel gating and entry into the desensitized state were affected. Evans blue also slowed the activation and the decay of glutamatergic miniature EPSCs (excitatory postsynaptic currents), demonstrating that receptor kinetics determine the time course of the synaptic response.

Animals↗
PubMed1992

Glutamate selectively increases the high-threshold Ca2+ channel current in sensory and hippocampal neurons.

Previous studies resulted in conflicting conclusions that glutamate application either decreases or increases the activity of Ca2+ channels in hippocampal neurons. We studied whole-cell Ca2+ currents (ICa) in chick dorsal root ganglion neurons and rat hippocampal cells. For both cell types glutamate (1-30 microM) increased high-threshold Ca2+ current. It was independent of the charge carriers, Ca2+ or Ba2+. Low-threshold Ca2+ channel current and the fast sodium current were not changed with glutamate application. The effect developed within 1-2 min and then further facilitated after washout of the agonist. A second application of glutamate produced no additional increase in ICa. No changes in the time-course of whole-cell currents were observed, suggesting that glutamate recruits 'sleepy' Ca2+ channels. Whatever its mechanism, overlasting increase of ICa by glutamate may be important in neuronal plasticity.

Animals↗
PubMed1992

The selective action of quinacrine on high-threshold calcium channels in rat hippocampal cells.

1. The whole-cell patch-clamp technique has been used to examine Ca channel currents carried by Ba (IBa) in rat hippocampal neurones. 2. Quinacrine selectivity decreased the high-threshold current activated by membrane depolarization from a holding potential of -70 mV. Neither the low-threshold Ca channel current nor the fast tetrodotoxin (TTX)-sensitive sodium current were affected by quinacrine. 3. Bath application of quinacrine caused a dose-dependent reduction of the peak amplitude of IBa. This effect was fast, voltage-independent, reversible and had a Kd of 30 +/- 5 microM. 4. The quinacrine-induced block did not change the time-course and the voltage dependence of IBa activation and deactivation. The inhibition revealed no use-dependence, ruling out an open channel block by quinacrine. 5. p-Bromophenacyl bromide had no effect on IBa suggesting the lack of involvement of phospholipase A2 in the action of quinacrine. In addition, the quinacrine-induced block was not related to the calmodulin pathway and internal quinacrine did not affect the peak amplitude of IBa. 6. The effect of quinacrine on the amplitude of IBa was dependent of the external pH, and suggested that only the single-protonated form of the drug can bind to the channel receptor with a Kd of 3 microM. Quinacrine and other substituted acridines can thus be useful for pharmacological and structure-activity studies of Ca channels.

Animals↗
PubMed1992

Pharmacological characterization of calcium currents and synaptic transmission between thalamic neurons in vitro.

We recorded from pairs of cultured, synaptically connected thalamic neurons. Evoked excitatory postsynaptic currents (EPSCs) reversed at +17 mV and were blocked reversibly by 1 mM kynurenic acid, a glutamate receptor antagonist. NMDA and non-NMDA receptors mediated excitatory post-synaptic responses, as shown by selective block of EPSC components with 50 microM (+/-)-2-amino-5-phosphonopentanoic acid and 10 microM 6,7-dinitroquinoxaline-2,3-dione, respectively. Inhibitory postsynaptic responses were evoked less frequently and were blocked by the GABAA receptor antagonist (-)-bicuculline methochloride. The pharmacological profiles of whole-cell calcium currents and evoked EPSCs were compared. With 50 microM cadmium chloride (Cd), whole-cell low voltage-activated (LVA) calcium currents were reduced in amplitude and high voltage-activated (HVA) calcium currents and excitatory synaptic transmission were completely blocked. This suggests that the residual calcium influx through LVA channels into the presynaptic terminal does not suffice to trigger transmitter release. A saturating concentration of omega-conotoxin GVIA (omega-CgTx) (2.5 microM) blocked one-third of whole-cell HVA calcium currents and evoked EPSCs. The dihydropyridine nifedipine (50 microM) reversibly reduced whole-cell HVA calcium currents in a voltage-dependent manner but not excitatory synaptic transmission. Cd and omega-CgTx did not alter amplitude distributions of miniature EPSCs, demonstrating that the inhibition of synaptic transmission was due to block of presynaptic calcium channels. We conclude that excitatory glutamatergic transmission in thalamic neurons in vitro was mediated mainly by HVA calcium currents, which were insensitive to omega-CgTx and nifedipine.

Animals↗
PubMed1979

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↗
PubMed1979

Decrease of inhibitory driving force in crayfish stretch reception: a mechanism of the convulsant action of penicillin.

The effect of penicillin on the evoked IPSP was investigated in the isolated crayfish stretch receptor. The IPSP driving force (IPSP reversal potential minus membrane potential) was reduced in a dose-dependent fashion but, when necessary correction was made for the decrease in resting membrane conductance, the synaptic conductance was only slightly reduced. The possibility that a penicillin-induced intracellular acidification was responsible for the decrease in IPSP driving force is considered.

Animals↗
PubMed1978

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↗
PubMed1977

Calcium-dependent depression of a late outward current in snail neurons.

Neuron cell bodies of Helix pomatia were voltage-clamped with a 300-millisecond depolarizing test pulse (pulse II) delivered I second after a depolarizing conditioning pulse (pulse I). The outward current, measured 200 milliseconds after the onset of pulse. II, exhibited a strong depression that was dependent on the presence of pulse. I. The maximum depression of the pulse II outward current occurred when pulse I voltages lay in the range over which calcium influx is inferred to be greatest; depression of the pulse II current subsided as pulse I potentials approached the putative calcium equilibrium potential. In the presence of extracellular [ethylenebis(oxyethylenenitrilo)]tetraacetic acid (EGTA) or D600, the intensity of the pulse II current became largely independent of pulse I, approaching the values of maximal depression seen in normal Ringer solution. On the other hand, lowering the intracellular pH with extracellular carbon dioxide-carbonate buffer had no measurable effect on the outward currents. Other experiments showed that it is primarily the calcium-dependent, outward-current hump of the N-shaped late current-voltage curve that is depressed by presentation of the conditioning pulse. It was concluded that distinct from an early potassium-activating role, calcium entering during a depolarization leads, during a subsequent depolarization, to a depression of the calcium-activated potassium system that persists for many seconds.

Action Potentials↗
PubMed1977

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↗
PubMed1977

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↗
PubMed1976

Change of potassium activity associated with membrane current flow.

Potassium-sensitive liquid ion exchanger microelectrodes are capable of recording fast concentration changes. Under suitable conditions, changes in extracellular potassium can be quantitatively measured during spike activity or voltage clamp pulses of exposed neurons. Comparison between transferred charge during outward current and the amount of extra potassium outside the cell reveals a deficit in net outward current, which is brought about by a long-lasting inward current. This inward current is facilitated by preceding depolarization and its appearance adds to a true inactivation of the potassium system. This is an example of how ion exchanger microelectrodes can be used to differentiate between time ionic fluxes underlying membrane currents. They are also useful in examining relations between neuronal activity and extracellular changes in potassium ion concentration in the central nervous system. Due to restricted diffusion in its extracellular space transient changes in potassium activity remain quite localized for considerable time. This makes it possible to identify discrete fields of activated neurons and to compare changes of neuronal excitability with variations of extracellular potassium activity.

Animals↗
PubMed1976

[Potassium activity in the cat cortex: experimental epilepsy].

Two mechanisms are discussed which link extracellular potassium accumulation and epileptogenic neuronal hyperactivity in the cortex. The potassium concentration (aK) of the environment of a repetitively discharging membrane can increase sufficiently for a supra-threshold depolarization at afferent erminals. This can explain the finding of ectopic spike generation and the antidromic breakthrough in thalamo-cortical projections after a primary cortical discharge. Spread and recurrent enhancement of excitatory drives may be the result of this mechanism. Initiation and termination of seizure is not explained by potassium accumulation. There is a ceiling level in potassium of about 10 mequ/1 which is strictly maintained during normal as well as epileptiform activity. This level is probably not high enough for depolarizing inactivation of neuronal membranes. Stimulation of cortical afferents can have a dual effect on aK. After a primary shortlasting increase, aK can reach subnormal values. This is possibly brought about by a stimulated re-uptake of K+. Seizures can be initiated at these subnormal levels. The effect of the re-uptake e.g. hyperpolarization of terminal afferents and increase of evoked transmitter release is discussed for the initiation for paroxysmal activity.

Animals↗
PubMed1976

A voltage-sensitive persistent calcium conductance in neuronal somata of Helix.

1. An intracellular voltage clamp in conjunction with a patch pipette utilizing feed-back to monitor local current from the soma membrane were used to analyse transient and stationary currents in bursting pacemaker neurones in Helix pomatia and H. levantina. 2. A weak, net inward current flows during small (less than or equal 20 mV) depolarizations. This current exhibits slow activation kinetics, persistence during prolonged depolarization, and slow turning off at end of depolarization. Consequently, the steady-state current-voltage curve exhibits a region of negative resistance from about -55 to -35 mV. 3. The slow inward current and the negative resistance characteristic are rapidly and completely abolished by substitution of Co2+ or La3+ for Ca2+ and are partially blocked by the Ca-blocking drug D-600. Substitution of Tris or glucose for Na+ significantly reduces the inward current only after 15-20 min exposure, recovery being equally slow. 4. The inward current and the negative resistance characteristic of the I-V curve are greatly enhanced by Ba2+ substitution for Ca2+. This is ascribed in part to Ba2+ carrying current through the slow inward current channels and in part to a suppression of the late K+ current by Ba2+. 5. The inward current is also present in many non-bursting neurones but fails to appear as a net inward current due to short circuiting by a leakage current or by the delayed potassium current. In these cells the slow inward current contributes to inward going rectification. Replacement of Ca2+ with Ba2+ enhances the current so as to produce a net inward current during small depolarizations in these neurones. 6. It is concluded that the slow inward current is carried primarily by Ca2+ in the soma membrane of bursting pace-maker neurones and a number of non-bursting cells examined in the parietal ganglion of Helix. 7. The sensitivity to small depolarizations and persistence during prolonged depolarization suggests two roles for the Ca system in the generation of slow pace-maker oscillations. In this model the Ca system contributes to the slow depolarization which constitutes the onset of the pace-maker wave, and also contributes to the increment in [Ca] in which activates the Ca-sensitive K+ conductance responsible for repolarization. The inhibition of spontaneous bursting by Ca-blocking agents supports this model.

Animals↗