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H L Haas

Publications and source records attributed to H L Haas.

At least 19 recordsLinked to original sources
PubMed1992

Zinc (Zn2+) blocks voltage gated calcium channels in cultured rat dorsal root ganglion cells.

Dorsal root ganglion cells (DRGs) exhibit 3 types of voltage-dependent calcium channels. We have cultured DRGs from 2- to 4-day-old rat pups and obtained whole-cell patch-clamp recordings of calcium-channel currents after 1-5 days in culture. The calcium-channel currents (carried by barium) were recorded with tetrodotoxin (TTX) in the external solution. A cesium-based solution containing Na-ATP, HEPES and EGTA was used in the recording pipette. Cells were held at -80 mV and calcium channel currents were evoked by stepping to depolarized voltages. The divalent cation zinc (Zn2+) blocked sustained and transient voltage sensitive calcium channel currents. Onset of the blockade was fast and a steady-state was reached within 5-15 min, depending upon the concentration used. The IC50 for inhibition of the peak current evoked by a step depolarization from -80 mV to 0 mV (N plus L channels) for 80 ms was 69 microM Zn2+ and the Hill slope about 1. The calcium current evoked by a voltage step from -80 mV to voltages between -40 mV and -15 mV (T-type current) was more sensitive (> 80% block with 20 microM Zn2+). During wash the effect was only partly reversible in 50% of the neurons. Thus, Zn2+ is a potent blocker of voltage dependent calcium currents in mammalian neurons, especially of T-type currents.

Animals↗
PubMed1992

Actions of oxaprotiline in the rat hippocampal slice.

1. Recordings were obtained from transverse slices of rat hippocampus, which were placed in a perfusion chamber and superfused with oxygenated artificial cerebrospinal fluid. 2. The effects of 10 microM (+)- or (-)-oxaprotiline applied by the bath were examined on the population spike, postsynaptic excitability in low Ca2+-high Mg2+ medium, the epileptiform discharge in Mg2+-free medium and long-term potentiation (LTP). Only the last paradigm (LTP) was significantly enhanced by (+)-oxaprotiline. 3. In rats chronically injected with (+)-oxaprotiline, neither LTP nor the actions of a variety of neurotransmitters in low Ca2+-high Mg2+ medium were significantly altered. 4. Intracellular recordings showed a small depolarization (3.5 +/- 1.6 mV) in response to 10 microM (+)- or (-)-oxaprotiline. Neither input resistance nor inward rectification, long-lasting afterhyperpolarization or accommodation were significantly altered. 5. Acute application, but not chronic treatment with (+)-oxaprotiline affects long-term potentiation in the hippocampal slice, presumably due to an effect on gabaergic inhibition.

Action Potentials↗
PubMed1992

Vasoactive intestinal polypeptide modulates neuronal excitability in hippocampal slices of the rat.

Vasoactive intestinal polypeptide added at submicromolar concentrations to the perfusion fluid of rat hippocampal slices and slice cultures enhanced the excitability of CA1 and CA3 pyramidal cells in several ways. Specifically, cells were depolarized and the Ca(2+)- and cyclic AMP-dependent potassium conductance was blocked as demonstrated by reduction of the long-lasting afterhyperpolarization and the accommodation of firing. This was also found in tetrodotoxin-containing medium. In low Ca(2+)-high Mg2+ medium (in synaptic isolation) the firing rate was increased. Synaptic transmission was potentiated: extracellularly registered excitatory postsynaptic potentials and population spikes in response to stratum radiatum stimulation and intracellularly recorded excitatory postsynaptic potential-inhibitory postsynaptic potential sequences were enhanced. These results are in keeping with the known stimulation of adenylate cyclase by vasoactive intestinal polypeptide.

Animals↗
PubMed1992

Comparison of the actions of adenosine at pre- and postsynaptic receptors in the rat hippocampus in vitro.

1. Intracellular microelectrode recordings were used to study the cellular location, the receptor pharmacology, and the mechanism of action of adenosine on pyramidal cells and presynaptic axonal endings in area CA3 of organotypic hippocampal slice cultures. 2. Adenosine (bath applied at 50 microM) caused a 10-15 mV hyperpolarization of CA3 cells, as well as a 75-100% decrease in the amplitude of excitatory and polysynaptic inhibitory postsynaptic potentials (EPSPs and IPSPs). Adenosine had no effect on the amplitude of monosynaptic IPSPs elicited in the presence of excitatory amino acid receptor antagonists, but did reduce the amplitude of isolated EPSPs, elicited after blocking GABAA receptors and reducing subsequent epileptic bursts with excitatory amino acid receptor antagonists. These data indicate that adenosine receptors are located on excitatory, but not inhibitory, presynaptic elements. 3. The A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, bath applied at 200 nM) blocked the pre- and postsynaptic actions of adenosine. DPCPX had no effect on the amplitude of control synaptic responses, suggesting that there is no tonic activation of adenosine receptors in hippocampal slice cultures under control conditions. The A1 receptor agonists R-N6-phenylisopropyladenosine (R-PIA) mimicked all pre- and postsynaptic actions of adenosine. 4. Pertussis toxin pretreatment (500 ng/ml for 48 h) prevented adenosine from activating postsynaptic K+ conductance, but not from inhibiting EPSPs. In contrast, stimulation of protein kinase C with phorbol ester (phorbol 12, 13-dibutyrate, 1 microM for 10 min) reduced the presynaptic, but not the postsynaptic, actions of adenosine. 5. Barium (bath applied at 1 mM) blocked the adenosine-activated K+ conductance, but not the inhibition of isolated EPSPs by adenosine. 6. Adenosine at 0.03-1 microM reduced the frequency of, or blocked, spontaneous epileptiform bursting produced by bicuculline. DPCPX (200 nM) increased the rate of spontaneous bursting, consistent with a tonic activation of adenosine receptors during hyperactivity, and led to the development of prolonged ictal-like bursts, suggesting that the endogenous release of adenosine may contribute to the termination of epileptic bursts. 7. We conclude that adenosine acts at pre- and postsynaptic receptors which are pharmacologically indistinguishable. Postsynaptically, adenosine increases a barium-sensitive K+ conductance via a pertussis toxin-sensitive GTP-binding protein. The presynaptic action of adenosine must, however, be mediated by some other mechanism.

Adenosine↗
PubMed1991

4-aminopyridine and barium chloride attenuate the anti-epileptic effect of carbamazepine in hippocampal slices.

The exact mode of action of the anti-epileptic agent carbamazepine is unknown. In hippocampal slices in which epileptiform discharges were induced by addition of penicillin to the perfusion medium, the depressant effect of carbamazepine was attenuated by the potassium-channel blockers barium chloride (0.1 mM) and 4-aminopyridine (200 microM), which suggested that potassium fluxes might be involved in the mechanism of action of carbamazepine.

4-Aminopyridine↗
PubMed1991

Anticonvulsants do not suppress long-term potentiation (LTP) in the rat hippocampus.

Long-term potentiation (LTP) of population spikes in the CA1 area of rat hippocampus was induced by tetanic stimulation of stratum radiatum in slices kept submerged in a perfusion chamber. Addition of the two antiepileptic drugs phenytoin or the diazepine midazolam to the medium did not significantly alter this phenomenon within 22 min after the tetanus. The early enhancement (post-tetanic potentiation, PTP) was reduced only by phenytoin. Therefore an interaction of these drugs with N-methyl-D-aspartate (NMDA) receptors and LTP induction is unlikely.

Animals↗
PubMed1991

Acute effects of antidepressant drugs on long-term potentiation (LTP) in rat hippocampal slices.

The actions of three clinically effective antidepressant drugs with different pharmacological profiles were investigated in the CA1 area of rat hippocampal slices. Imipramine and (+) or (-)-oxaprotiline had negligible effects on population spikes evoked by stratum radiatum stimulation, but reduced postsynaptic excitability in low Ca high Mg medium after an exposure of more than 15 min. Imipramine and (+)-oxaprotiline at 10 mumol/l enhanced long-term potentiation (LTP) when a lower stimulation strength was applied while (+)-oxaprotiline reduced LTP when a higher stimulus amplitude was used to evoke population spikes. (-)-oxaprotiline (levoprotiline) had a similar effect which was, however, not significant in either stimulation paradigm at the P less than 0.05 level. Imipramine actions were also studied on epileptiform discharges in Mg(2+)-free medium: a facilitation-inhibition sequence with a slow time course was seen with 50 mumol/l but no effect with 10 mumol/l. An involvement of N-methyl-D-aspartate (NMDA)-receptors in acute actions of antidepressants is unlikely but long-term potentiation in the hippocampus is modulated by these drugs.

Action Potentials↗
PubMed1991

Properties of tuberomammillary histamine neurones and their response to galanin.

Histaminergic neurones in the tuberomammillary nucleus possess electrophysiological properties which distinguish them from other neurones in their neighborhood. Their resting potential is -50 mV and they are spontaneously active at about 2 Hz in a slice preparation. They display a transient outward rectification and an anomalous inward rectification. Bath application of galanin (0.1 microM) reduced their firing rate significantly and hyperpolarized them slightly.

Action Potentials↗
PubMed1990

An electrophysiological study of the ontogenesis of adenosine receptors in the CA1 area of rat hippocampus.

The depressant effect of adenosine (Ad) was studied electrophysiologically in hippocampal slices from 5-, 10-, 15-, 20-, 30- and 120-day-old rats. Ad (10 microM) depressed the field EPSP in CA1 to the same extent in all age groups. Caffeine (Caf), an Ad receptor antagonist, enhanced and nitrobenzylthioinosine (NBI), an Ad uptake blocker, depressed the field EPSP. Both these effects were, however, less prominent in slices from younger animals, a finding consistent with lower extracellular levels of endogenous Ad in neonatal rats.

Action Potentials↗
PubMed1990

Effects of histamine on dentate granule cells in vitro.

Hippocampal slices from rat brain were exposed to histamine and related substances in a perfusion chamber. Granule cells of the dentate gyrus were studied with conventional extra- and intracellular recording and a single electrode voltage clamp. Histamine caused, through activation of H(2)-receptors, a small depolarization, an increase in the number of synaptic and action potentials, a block of the long lasting (but not the early) component of spike afterhyperpolarizations and a reduction of the accommodation of action potential firing. These effects were mimicked by forskolin (suggests activation of adenylate cyclase). In voltage clamp, histamine blocked a long lasting calcium-dependent outward tail current without any reduction of inward current. Thus histamine selectively blocks the late calcium-dependent potassium current in dentate granule cells which receive histaminergic input from the posterior hypothalamus. Histamine also reduces the field excitatory postsynaptic potential evoked by perforant path stimulation. These actions allow for a powerful modulation of excitatory signals and an effective regulation of hippocampal excitability.

Action Potentials↗
PubMed1990

Two transient outward currents in histamine neurones of the rat hypothalamus in vitro.

1. The transient outward current exhibited by the histamine neurones of the tuberomammillary nucleus was studied using the single-electrode voltage clamp technique in an in vitro rat hypothalamic slice preparation. 2. The transient outward current exhibited steady-state inactivation at the resting potential. Inactivation was removed by priming hyperpolarization with a V1/2 of -85 +/- 1.2 mV, while the V1/2 for activation was -60.3 +/- 2.1 mV. 3. The decay of the transient outward current was best fitted by two exponentials with time constants of 104 +/- 36 and 568 +/- 128 ms. These two components were provisionally termed IA,f and IA,s for the fast and slowly decaying currents, respectively. 4. Removal of inactivation was time dependent; inactivation was fully removed by hyperpolarizing pulses to -110 mV of 200 ms or greater duration. Removal of inactivation of IA,f was rapid, becoming complete with hyperpolarizing pre-pulses of 50 ms or greater, while removal of inactivation of IA,s was not complete until hyperpolarizing pre-pulses were 200 ms in duration. 5. The fast decaying current IA,f was selectively blocked by 1 mM-4-aminopyridine. Tetraethylammonium chloride (10 mM) had no effect on either IA,f or IA,s. 6. The inactivation curves for IA,s, determined both by using the values obtained from the amplitude of the computed slower exponential function as well as that of the current remaining in 1 mM 4-aminopyridine, were negative to those of IA,f. Similarly derived activation curves for IA,s were positive to those of IA,f. 7. Superfusion with a nominal 0 Ca2+ medium containing 10 mM-Mg2+ did not reduce the maximal transient outward current. 8. The reversal potential of IA,s with 2.5 mM-K+ in the medium was -95 +/- 3 mV; the reversal potential of IA,f was at least 15 mV negative to that of IA,s. 9. It is concluded that histaminergic tuberomammillary neurones possess at least two transient outward currents which can be distinguished on the basis of their rates of decay, 4-aminopyridine sensitivity, voltage dependence and reversal potentials.

4-Aminopyridine↗
PubMed1989

Hippocampal mossy fiber distribution and long-term potentiation in two inbred mouse strains.

We studied long-term potentiation in the inbred mouse strains DBA/2 and C3H/He known to be different in both hippocampal mossy fiber distribution and several aspects of learning. Tetanic stimulation of mossy fibers resulted in a significantly stronger increase of the population spike amplitude in the CA3 pyramidal cell layer of C3H mice. This result suggests that the extent of the CA3 hippocampal mossy fiber projection correlates with synaptic efficacy in mice.

Action Potentials↗
PubMed1989

Cholinergic activation of medial pontine reticular formation neurons in vitro.

In vivo microinjections of cholinergic compounds into the medial pontine reticular formation have produced some or depending on the injection site, all of the phenomena of REM, thus providing the only adequate pharmacological model of this behavioral state. The necessary anatomical substrate, a cholinergic projection to the mPRF was recently demonstrated, however the direct effect of cholinergic agonists on mPRF neurons is unknown. We have examined the effects of carbachol on mPRF neurons recorded in vitro from brainstem slices of Sprague-Dawley rats (8-10 days old). Three kinds of response to the application of carbachol (0.5-1 microM) were observed (n = 15) as follows: a depolarizing response (67%), a hyperpolarizing response (20%) and a biphasic response consisting of a hyperpolarizing response followed by a depolarizing response (13%). Under voltage clamp control, the depolarizing response was observed as an inward current resulting from a decrease in conductance which was constant over the membrane potential range of -100 to -50 mV. Reversal potential was negative to -80 mV. An increase in the excitability of neurons (as measured by responses to identical intracellularly applied depolarizing current pulses) during the depolarizing responses was due to the increase in steady state inward current. When intracellular DC current of equal amplitude but opposite polarity was applied, no increase in excitability was observed. This response was always blocked by the addition of atropine (0.5-1 microM) to the perfusate. The hyperpolarizing response was observed as an increase in outward current due to an increase in conductance with marked voltage sensitivity (over the range of -100 to -50 mV) characteristic of the anomalous rectifier. Preliminary data indicated that the hyperpolarizing response was more sensitive to pirenzepine (complete blockade at 1.0 microM) than the depolarizing response (complete blockade at 2 microM) but neither response was affected by pirenzepine concentrations of 200 nM or less. Cholinergic effects on evoked depolarizing PSPs were examined on neurons with depolarizing (n = 3) and biphasic (n = 1) responses and in all cases, the PSPs were enhanced. This enhancement was blocked by atropine. In conclusion, it is suggested that activation of two different muscarinic receptors (neither of which is the M1 receptor) on mPRF neurons results in two different responses, a decrease in a voltage-insensitive potassium conductance and an increase in the anomalous rectifier.

Acetylcholine↗
PubMed1989

Action of anticonvulsants on hippocampal slices in Mg-free medium.

The effects of six prototype anticonvulsant drugs were investigated on epileptiform field potential discharges evoked in hippocampal slices of rats by removing magnesium ions from the perfusion fluid in order to reveal a possible interaction with N-methyl-D-aspartate (NMDA) receptor activation. All drugs reduced the multiple discharges with the following order of potency: midazolam greater than carbamazepine = phenytoin = phenobarbital greater than ethosuximide = valproate. They had a stronger depressant effect on the later population spikes but none of them abolished the epileptiform discharge. These effects can be explained by known mechanisms of action of the anticonvulsants tested and lend no support for a specific interaction with NMDA receptors.

Animals↗
PubMed1989

The brain histamine system in vitro.

The electrophysiological properties of identified tuberomammillary histamine neurones were investigated in explant and slice preparations. The effects of histamine were studied on target neurones, mainly in the hippocampal slice. The results describe an important modulatory role of this diffusely projecting system.

Action Potentials↗
PubMed1989

Characterization of inhibition mediated by adenosine in the hippocampus of the rat in vitro.

1. Intracellular recordings with single-electrode voltage clamp were employed to study the mechanism of adenosine-elicited inhibition of CA1 neurones of the rat in vitro. 2. Adenosine elicits a steady-state outward current in association with an increase in conductance. The driving force varied with external potassium concentration as predicted by the Nernst equation for a change primarily in potassium permeability. 3. Adenosine current was blocked by high concentrations of 4-aminopyridine or barium. In the majority of neurones this current was voltage insensitive. In the remainder, the current was inwardly rectifying. The rectification was blocked by tetraethylammonium. 4. When the adenosine-elicited potassium current was blocked, slow inward currents, normally carried by calcium, were unaffected by adenosine. We conclude that this adenosine inhibition is mediated by an increase in a voltage- and calcium-insensitive potassium conductance in CA1 neurones.

4-Aminopyridine↗
PubMed1988

Effects of purinoceptor agonists on electrophysiological properties of rat mesencephalic trigeminal neurones in vitro.

Intracellular recordings were performed in a midpontine slice preparation of the rat brain containing the mesencephalic trigeminal nucleus (MTN). In spite of the previous demonstration of an adenosine deaminase-containing plexus terminating on this nucleus, adenosine, adenosine 5'-triphosphate (ATP), alpha,beta-methylene ATP (alpha,beta-meATP) and 2-methylthio ATP all failed to influence the membrane potential or input resistance of the MTN cells. Moreover, there was no apparent change in the shape of action potentials in the presence of these drugs, and the accomodation of the firing rate to depolarizing pulses was not affected either.

Action Potentials↗