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H L Haas

Publications and source records attributed to H L Haas.

At least 55 records · Page 3Linked to original sources
PubMed1998

High-affinity copper block of GABA(A) receptor-mediated currents in acutely isolated cerebellar Purkinje cells of the rat.

The actions of Cu2+ ions on GABAA receptor-mediated currents in acutely isolated Purkinje cells from rat cerebellum were studied using the whole-cell patch-clamp technique and a rapid perfusion system. Bath application of Cu2+ reduced currents induced by 2 microM gamma-aminobutyric acid (GABA) in a concentration-dependent manner with an IC50 of 35 nM. The Cu2+-induced block of GABA responses was not voltage-dependent. Increasing the GABA concentration (from 2 to 50 microM) decreased the blocking effect of Cu2+. Dose-response analysis for activation of GABAA receptors revealed a twofold decrease in apparent affinity for GABA in the presence of 0.1 microM Cu2+. Recovery from the block required several minutes after removal of Cu2+ from the medium. The block was removed by histidine, which preferentially forms complexes with Cu2+, or by other chelating substances. Application of 10 microM histidine immediately before application of 2 microM GABA completely relieved the block of GABA responses produced by 0.1 microM Cu2+. The effect of histidine was concentration-dependent with an EC50 of 0.75 microM. The results demonstrate that Cu2+ is a potent inhibitor of GABA-evoked responses in rat Purkinje cells. Copper may be an endogenous synaptic modulating factor. Cu2+ toxicity, notably in Wilson's disease, could result to some extent from chronic GABAA receptor blockade.

Animals↗
PubMed1997

Adenosine A1 receptor-mediated depression of corticostriatal and thalamostriatal glutamatergic synaptic potentials in vitro.

Electrophysiological recordings in rat brain slices have been used to study the actions of adenosine on striatal neurons and striatal excitatory amino acid neurotransmission originating in the cortex or the thalamus. Adenosine had no effects on membrane properties of striatal neurons. Adenosine and the A1 agonist N6-Cyclopentyl adenosine reduced EPSPs of both cortical and thalamic origin by more than 50%. Depression of EPSPs was associated with an increase in paired-pulse facilitation, suggesting a presynaptic locus of action. EPSP depression was blocked by the A1 antagonist, 8-Cyclopentyl-1,3-dipropyl xanthine. The A2 agonist 5'-(N-cyclopropyl)-carboxamidoadenosine had no effect on excitatory amino acid neurotransmission. The A1 antagonist alone enhanced the synaptic component of the evoked field potential (23 +/- 12%). These results indicate that endogenous adenosine, acting via A1 receptors, limits striatal glutamatergic neurotransmission, serving a modulatory and neuroprotective role.

Adenosine↗
PubMed1997

5-HT inhibits lateral entorhinal cortical neurons of the rat in vitro by activation of potassium channel-coupled 5-HT1A receptors.

Serotonin (1-40 microM) reduced input resistance by 20.6 +/- 6% and hyperpolarized stellate and pyramidal neurons of layers two and three of the lateral entorhinal cortex. 5-Carboxamidotryptamine, a 5-HT1 agonist, and the selective 5-HT1A agonist 8-hydroxy-dipropylaminotetralin mimicked the action of serotonin. The reversal potential of 5-HT-mediated hyperpolarizations was sensitive to the extracellular K+ concentration, indicating a potassium conductance change. Serotonin treatment suppressed excitatory amino acid-mediated synaptic potentials (by 48%, Kd = 6.9 microM) and responses to exogenously applied glutamate (70.1 +/- 17% of control, n = 7), but did not alter paired-pulse facilitation, indicating a postsynaptic site of action. Intracellular application of QX-314, a blocker of potassium conductance, significantly reduced depression of synaptic potentials by 5-HT agonists. In cells filled with QX-314, responses to exogenously applied glutamate were not reduced by serotonin or 5-carboxamidotryptamine application. These results indicate that the observed conductance increase associated with 5-HT application accounts for most if not all of the observed depressant effects of 5-HT1A agonists on excitatory amino acid-mediated neurotransmission.

2-Amino-5-phosphonovalerate↗
PubMed1997

Suppression of long-term potentiation in hippocampal slices by copper.

Cu(2+)-ions are known to interfere with gamma-aminobutyric acid (GABA)- and glutamate-operated ion channels from experiments with isolated neurons. Such actions are likely involved in the pathophysiology of Wilson's disease. We have now studied the effects of Cu2+ in the CA1 region of hippocampal slices. Field excitatory postsynaptic potential (EPSP) slopes in the CA1 region were unaffected by 1 microM Cu2+ but were depressed by 10 microM (to 85%) and 100 microM (to 50%). A paired-pulse test revealed no difference in facilitation in the presence or absence of Cu2+, indicating a postsynaptic action. A late component of intracellularly registered EPSPs in Mg(2+)-free solution was also reduced by Cu2+. The N-methyl-D-aspartate (NMDA) component of the field EPSP, isolated by adding CNQX and bicuculline in Mg(2+)-free solution, was reduced to 69% of control by 1 microM and to 50% of control by 10 microM Cu2+. Long-term potentiation, evoked by 3 x 50 pulses at 100 Hz, 20 s interval amounted to 132 +/- 11% 90 min after tetanization under control conditions but was absent in the presence of 1 microM Cu2+ in the bath. Thus low concentrations of copper can selectively reduce NMDA-mediated potentials and synaptic plasticity.

Animals↗
PubMed1997

Histamine H1 receptors in C6 glial cells are coupled to calcium-dependent potassium channels via release of calcium from internal stores.

We investigated the action of histamine on C6-astroglioma cells using patch clamp recording and intracellular calcium measurement. Application of 100 microM histamine hyperpolarized the resting membrane potential and increased free intracellular calcium. Membrane hyperpolarization was accompanied by a decrease in input resistance. The effect of histamine was reversible and responses persisted following repeated applications. In voltage clamp experiments histamine elicited an outward current associated with a conductance increase and a reversal potential near the Nernst potential for potassium. The action of histamine was blocked by mepyramine but not by cimetidine or thioperamide suggesting that a H1 receptor mediated the response. Quinidine and charybdotoxin, but not apamin, blocked the hyperpolarization. Buffering internal calcium with BAPTA diminished the activation of the potassium channel, suggesting a calcium-dependent K(+)-channel, which was also found to be regulated by protein kinase C and phosphatases. The increase in intracellular calcium was not dependent on external calcium or sensitive to pertussis toxin, cholera toxin, forskolin or 8-bromo-cAMP. Both the hyperpolarization and the increase in intracellular calcium were blocked by thapsigargin or the phospholipase C inhibitor U73122. These results indicate that histamine liberates calcium from internal stores by activation of phospholipase C which in turn leads to an increase of intracellular Ca2+ and thereby to the activation of a calcium-dependent potassium channel in C6 glial cells.

Animals↗
PubMed1997

Activation of interneurons at the stratum oriens/alveus border suppresses excitatory transmission to apical dendrites in the CA1 area of the mouse hippocampus.

The consequences of activation or inactivation of interneurons at the CA1 stratum oriens/ alveus border for signal transmission at the apical dendritic region of pyramidal cells were investigated in slices from mice submerged in a perfusion chamber. A characteristic subpopulation of interneurons with a horizontal dendritic tree in this region, which sends a GABAergic projection to the apical dendrites of CA1 pyramidal cells is strongly excited by metabotropic glutamate receptor activation and receives GABAergic input from vasoactive intestinal polypeptide-containing interneurons. Pressure ejection of glutamate or the metabotropic agonist 1s,3r-aminocyclopentane dicarboxylic acid from micropipettes onto the stratum oriens/alveus border caused a long lasting (more than 90 min) decrease of field-excitatory postsynaptic potentials in the strata radiatum and lacunosum-moleculare. The GABAB antagonist CGP 35348 (100 microM in the perfusion fluid) partially and reversibly blocked this effect. Vasoactive intestinal polypeptide- (0.1 microM in the bath) excited neurons with response and firing properties characteristic for interneurons at the oriens/alveus border. Local pressure application of vasoactive intestinal polypeptide (10 microM) to the alveus region led, after a brief (2 min) and small (10%) increase, to a longer lasting (30-50 min) decrease (by 20-30%) in the slope of the field-excitatory postsynaptic potential in strata radiatum and lacunosum-moleculare. This action was completely blocked by bath application of CGP 35348. Local application of tetrodotoxin in the stratum oriens/alveus region markedly increased the slope of evoked dendritic excitatory postsynaptic potentials, and caused multiple firing of pyramidal cells. Thus, stratum oriens/alveus interneurons have a profound inhibitory effect on signal transmission in the apical dendritic area of CA1, which is, at least in part, mediated by GABAB receptors. It appears that the GABAB receptor-mediated effect in stratum lacunosum-moleculare is produced by vasoactive intestinal polypeptide-sensitive interneurons.

Animals↗
PubMed1997

Histaminergic system in co-cultures of hippocampus and posterior hypothalamus: a morphological and electrophysiological study in the rat.

Neurons of the tuberomammillary nucleus in the posterior hypothalamus diffusely project to most parts of the central nervous system, where their main transmitter, histamine, modulates the excitability of the target neurons. The development of a histaminergic hypothalamo-hippocampal pathway and its function were studied in organotypic co-cultures. Immunocytochemistry for histidine decarboxylase, the specific synthesizing enzyme, stained clusters of neurons in the hypothalamic tuberomammillary area. Immunolabelled varicose processes innervated the co-cultured hippocampus and established a few synaptic contacts on dendrites. Cultured tuberomammillary neurons displayed their typical membrane properties and were spontaneously active. In hippocampal pyramidal cells of the CA3 region the long-lasting afterhyperpolarization was reduced by histamine or impromidine and increased by the H2 antagonist cimetidine, but not by the H1 antagonist mepyramine. The membrane potential was depolarized in presence of an H2 agonist and hyperpolarized by an H2 antagonist. In single hippocampal cultures histamine antagonists did not affect afterhyperpolarization and membrane potential. Histaminergic neurons retain their main morphological and physiological characteristics in slice cultures and establish a functional connection with co-cultured target cells.

Animals↗
PubMed1996

Calcium-dependent prepotentials contribute to spontaneous activity in rat tuberomammillary neurons.

1. Intracellular recordings from histaminergic neurons of the tuberomammillary (TM) nucleus reveal subthreshold depolarizing potentials (DPs) which persist in the presence of tetrodotoxin. 2. Block of hyperpolarization-activated current by 1-4 mM Cs+ failed to reduce spontaneous activity or DPs. 3. In the presence of tetrodotoxin DPs are voltage dependent and are depressed by Cd2+ and Co2+. 4. Ba2+ (100 microM) treatment enhances DP amplitude and converts low-amplitude potentials to tetrodotoxin-insensitive action potentials. 5. In the presence of TTX, DPs are reduced by Ni2+. Spontaneous action potentials are also reduced by Ni2+ (100-300 microM). A low-threshold Ca2+ current is present which is sensitive to Ni2+. These results indicate the presence of calcium currents, perhaps of the low-threshold type, which contribute to activation of action potentials in TM neurons.

Action Potentials↗
PubMed1996

Alpha-bungarotoxin-sensitive nicotinic responses in rat tuberomammillary neurons.

Application of acetylcholine (ACh), nicotine or 1, 1-dimethyl-4-phenylpiperazinium elicited an inward current in histaminergic neurons of the tuberomammillary nucleus. These responses were blocked by 25-50 nM alpha-bungarotoxin. Acutely dissociated neurons from the tuberomammillary nucleus displayed fast, desensitizing responses to ACh. ACh-activated currents exhibited rectification at positive membrane potentials. The Hill coefficient and half-maximally effective concentration (EC50) for ACh were 1.85 and 119 microM, respectively. Desensitization could be fitted by an exponential. Preincubation in low concentrations of ACh diminished subsequent responses to higher concentrations of ACh. The alpha-bungarotoxin sensitivity in conjunction with the low potency of ACh at this receptor are consistent with its identification as an alpha7-subunit-containing receptor. These alpha-bungarotoxin-sensitive receptors are ligand-gated cationic channels which are not thought to play a role in synaptic transmission, but they may be an important site for central actions of nicotine.

Acetylcholine↗
PubMed1996

A simple perfusion system for patch-clamp studies.

Many systems for rapid perfusion of isolated cells or membrane patches operate with separate capillaries for each drug to be applied. We describe here a simple way by which the solutions in a single capillary can be quickly exchanged during recording. The device consists of a 100 microliters reservoir mounted 20 mm above the preparation and a capillary through which test perfusion media are driven by gravity. The application system is used for preparations attached to a recording pipette and includes two capillaries with solution exchange capabilities within a larger bath tube; it is driven by a capstan motor which is held in a neutral position by a spring. An unlimited number of solutions can be applied through each channel. The volume for washing and refilling a channel is typically 0.5 ml; it may be as low as 0.1 ml. The time interval necessary for sequential applications of different solutions through the same channel is less than 20 s. The solution flows through the capillaries and the bath tube at a speed of about 3 mm/s (30 and 600 nl/s respectively). The mechanical displacement for concentration jumps is adjustable from 0 to 0.4 mm in two directions and can be set to occur within 2-100 ms.

Animals↗
PubMed1996

Extracellular adenosine levels in neostriatum and hippocampus during rest and activity periods of rats.

Adenosine is an inhibitory modulator in the mammalian brain with a possible role in sleep regulation, which is mainly indicated by pharmacological studies showing that adenosine or its analogs can induce sedation and sleep, whereas adenosine antagonists, like caffeine and theophylline, are potent behavioral and neuronal stimulants. In contrast to these pharmacological findings, data on endogenous adenosine in relation to sleep and waking are sparse. Therefore, we have now used in vivo microdialysis to investigate the extracellular levels of adenosine in the neostriatum and hippocampus of freely moving rats. Adenosine was monitored over a time course of 24 h, during which the animals were exposed to a 12 h day/night rhythm with lights-off from 19.00 to 07.00. In this lights-off period, i.e. the rats' active period, the maximal levels of neostriatal and hippocampal extracellular adenosine were higher than during the lights-on period. In contrast to the neostriatum, extracellular levels of hippocampal adenosine tended to increase towards the end of the lights-off period, reaching its maximal level at 07.00, and decreasing again within the following hour. The changes of hippocampal adenosine levels were related to behavior, since significant increases in "sleep-like" behavior, as well as decreases in overall movements and consummatory behavior, were observed when adenosine levels had reached their maxima in the hippocampus; no such relationship was found with respect to the neostriatum. These results are in keeping with a role of endogenous adenosine in the regulation of sleep and wakefulness, and point to a specific role of adenosine in the hippocampus. They also raise the possibility that adenosine may be involved in different behavioral processes dependent on the area of the brain, as well as the type of adenosine receptor involved. Finally, given the known evidence for neuroprotective actions of adenosine, its accumulation in the hippocampus as a function of behavioral activity may serve to prevent or repair the neural degenerative consequences of such activity. It is proposed that adenosine's sleep-promoting effects result from its signalling to cease behavioral activity in order to prevent excessive activity-related changes, and thus allow other restorative sleep-related processes to take over.

Adenosine↗
PubMed1996

Voltage-activated calcium channel currents of rat DRG neurons are reduced by mercuric chloride (HgCl2) and methylmercury (CH3HgCl).

The actions of bath applied mercuric chloride (HgCl2) and methylmercury (CH3HgCl) on voltage-activated calcium channel currents (VACCCs) were tested, using the whole cell patch clamp recording technique with cultured dorsal root ganglion (DRG) neurons from 2-4 day old rat pups. Both metal compounds reduced the current irreversibly in a concentration dependent fashion, reaching a new (lower) steady state within 3 to 5 min after application. Inorganic mercury was more effective in reducing the VACCCs with an IC50 of 1.3 microM, while the IC50 for methylmercury was 2.6 microM. But the threshold concentrations were below 0.25 microM for both metal compounds and the calcium channel currents were reduced by more than 90% with concentrations of 5 microM and 20 microM, respectively. The Hill coefficient for both dose-response relationship was calculated as approximately 1. Calcium channel currents were reduced over the entire voltage range, but the current-voltage relation shifted to more positive potentials in a concentration dependent manner, the effect being more pronounced with HgCl2 than with CH3HgCl (1 microM HgCl2: 10 mV shift, 5 microM CH3HgCl: 5 mV shift). At higher concentrations (> or = 2 microM for HgCl2, and > or = 10 microM for CH3HgCl) an unidentified membrane current was observed. The inorganic mercury caused an inward current, while the organic mercury compound generated a biphasic current with a transient inward and a long lasting outward component. Our results suggest that mercury compounds affect the electrical properties of neurons and thereby decrease cognitive and motor performance.

Animals↗
PubMed1995

pH-dependent modulation of N-methyl-D-aspartate receptor-mediated synaptic currents by histamine in rat hippocampus in vitro.

Modulation of excitatory postsynaptic currents by histamine was examined using whole cell recording methods in the CA1 region of slices of rat hippocampus. Histamine affected the N-methyl-D-aspartate (NMDA) component of the synaptic current in a pH-dependent manner: at lowered pH (7.2) it enhanced the NMDA-mediated synaptic currents while at raised pH (7.6) it reduced them. At a pH of 7.4 there was no significant action of histamine. Histamine failed to alter the non-NMDA component of the synaptic current. These results indicate that histamine acts at a postsynaptic site to modulate NMDA mediated synaptic currents in a pH dependent manner. This mechanism may have important implications for the pathophysiology of shifts in extracellular pH.

Animals↗
PubMed1995

pH-dependent facilitation of synaptic transmission by histamine in the CA1 region of mouse hippocampus.

The action of histamine on excitatory synaptic transmission in the CA1 region of the mouse hippocampus was investigated. In a medium at pH 7.4 population spikes were increased for approximately 60 min after a brief (5 min) perfusion with histamine (5 microM) but excitatory postsynaptic potentials (EPSPs) were unaffected, as previously reported in the rat. At pH 7.0, however, a late component of extra- and intracellularly registered EPSPs was enhanced in two phases: a shorter (by 30%) and a longer lasting one (> 1 h by 10%). The NMDA antagonist amino-phosphonovalerate (60 microM) blocked this late component and prevented the EPSP broadening by histamine. In some cells histamine induced burst-firing and prolonged EPSPs. The actions on EPSPs were not mediated by any of the known histamine receptors as they were not mimicked by histamine H1, H2 and H3 agonists or blocked by H1, H2 or H3 antagonists. We conclude that histamine enhances a late (NMDA) component of hippocampal EPSPs when protonization is increased by a slight shift of the pH in the acidic direction. Such shifts occur during intense nervous discharges, e.g. in epileptic tissue or following tetanic stimulation, and in hypoxic conditions.

Animals↗
PubMed1995

Subcortical modulation of synaptic plasticity in the hippocampus.

A two-stage model of memory trace formation in the hippocampus considers exploratory behavior associated with theta activity and consumatory behaviors or immobility associated with the occurrence of synchronous pyramidal cell discharges. Threshold, frequency and extent of CA3 bursts differ between differently performing strains of mice and are subject to subcortical modulation. Mechanisms for such actions are described: interference with potassium and other cation channels through second messengers and a direct action of histamine on the NMDA receptor channel. Furthermore long-lasting potentiations of synaptic transmission and excitability following brief exposures of hippocampal slices to histamine, noradrenaline, and serotonin are mediated by cyclic AMP and presumably protein kinase A.

Animals↗