Biomedical subjects

U Gerber

Publications and source records attributed to U Gerber.

At least 37 records · Page 2Linked to original sources

PubMed1994

Potentiation of a metabotropic glutamatergic response following NMDA receptor activation in rat hippocampus.

Interactions between metabotropic glutamate and N-methyl-D-aspartate (NMDA) receptor-mediated responses were investigated in hippocampal CA3 cells using the single electrode voltage-clamp method. Bath application (2.5-10 microM, 30 s) or iontophoresis of 1-amino-cyclopentyl-trans-1S,3R-dicarboxylate (ACPD), a selective agonist for metabotropic glutamate receptors, resulted in an inward current associated with a decrease in membrane conductance. Following transient bath application of NMDA (5-10 microM, 30-60 s), the ACPD-induced inward current was potentiated for a period of up to 25 min (by 61 +/- 8% with bath application, by 32 +/- 15% with iontophoresis). Transient application of NMDA did not result in a potentiation of ionotropic RS-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) or metabotropic muscarinic responses. ACPD responses were not potentiated following transient AMPA application. Intracellular buffering of calcium with tetrapotassium bis(O-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid (BAPTA) prevented potentiation by NMDA in all cells. Bath application of arachidonic acid did not mimic the NMDA-induced potentiation. These results demonstrate that activation of NMDA receptors can specifically induce a long-lasting potentiation of a metabotropic glutamatergic response in hippocampal CA3 pyramidal cells. The characterization of this interaction may contribute to the elucidation of the physiological significance of metabotropic glutamate receptors.

Animals↗

PubMed1994

GABAB and adenosine receptors mediate enhancement of the K+ current, IAHP, by reducing adenylyl cyclase activity in rat CA3 hippocampal neurons.

1. Gamma-aminobuturic acid-B (GABAB) and adenosine A1 receptors, which are expressed in hippocampal pyramidal cells, are linked to pertussis toxin-sensitive G-proteins known to be coupled negatively to the enzyme adenylyl cyclase. This study investigates the electrophysiological consequences of adenylyl cyclase inhibition in response to stimulation of these receptors. 2. Single-electrode voltage-clamp recordings were obtained from CA3 pyramidal cells in rat hippocampal slice cultures in presence of tetrodotoxin. The calcium-dependent potassium current (IAHP), which is very sensitive to intracellular levels of adenosine 3',5'-cyclic monophosphate (cAMP), was used as an electrophysiological indicator of adenylyl cyclase activity. 3. Application of baclofen (10 microM), a selective agonist at GABAB receptors, or adenosine (50 microM) each resulted in a transient decrease followed by a significant enhancement in the amplitude of evoked IAHP. The initial reduction in amplitude of IAHP probably reflects inadequacies in voltage clamp of electronically distant dendritic sites, due to the shunting caused by concomitant activation of potassium conductance by baclofen/adenosine. Comparable increases in membrane conductance in response to the GABAA agonist, muscimol, caused a similar reduction in IAHP. The enhancement of IAHP is consistent with an inhibition of constitutively active adenylyl cyclase. 4. The receptor mediating the responses to adenosine was identified as belonging to the A1 subtype on the basis of its sensitivity to the selective antagonist 8-cyclopentyl-1,3-dipropylxanthine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗

PubMed1993

Inhibition of a slow synaptic response by a metabotropic glutamate receptor antagonist in hippocampal CA3 pyramidal cells.

The effects of a novel antagonist of metabotropic glutamate receptors were investigated in CA3 pyramidal cells in hippocampal slice cultures of the rat. Earlier experiments showed that selective activation of metabotropic glutamate receptors with low concentrations of an agonist, 1S, 3R-1-amino-cyclopentane-1,3-dicarboxylic acid (ACPD), induced an inward current associated with a decrease in membrane conductance and inhibition of the slow calcium-dependent potassium current. These responses were strongly and reversibly reduced by the antagonist, (RS)-alpha-methyl-4-carboxyphenylglycine (MCPG, 0.5-1 mM). In the presence of antagonists of ionotropic glutamate receptors, stimulation of the afferent mossy fibres evoked postsynaptic responses in CA3 pyramidal cells which paralleled those observed with exogenously applied metabotropic glutamate receptor agonists, i.e. a slow inward current and a reduction of calcium-dependent potassium current. Both responses were greatly reduced by bath-applied MCPG (1 mM). These results show that MCPG acts as an effective antagonist at metabotropic glutamate receptors coupled to potassium conductances in the hippocampus. Furthermore, they confirm that glutamate release from presynaptic terminals can modulate postsynaptic properties by activation of metabotropic glutamate receptors.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1993

Interaction of zinc with ionotropic and metabotropic glutamate receptors in rat hippocampal slices.

The actions of zinc on ionotropic and metabotropic glutamate receptors were studied using intracellular recording in acutely prepared adult rat hippocampal slices and in organotypic hippocampal slice cultures. In control Krebs, glutamate and non-N-methyl-D-aspartate (NMDA) agonist-induced responses were enhanced by zinc (25-300 microM). However, under conditions favouring NMDA receptor activation, zinc inhibited glutamate- and NMDA-induced responses. Metabotropic glutamate receptor-mediated responses activated in cultured slices by 1-amino-cyclopentane-1,3-dicarboxylate (1S,3R-ACPD) or by quisqualate, were reversibly inhibited by zinc (200 microM). These results indicate that zinc can inhibit responses induced by activation of metabotropic glutamate receptors and reaffirm that zinc has a differential effect on NMDA and non-NMDA receptors.

Animals↗

PubMed1993

Nicotinic depolarizations of rat medial pontine reticular formation neurons studied in vitro.

Either muscarinic or nicotinic cholinergic activation of the medial pontine reticular formation evokes a behavioral state, indistinguishable in most respects from that of natural rapid eye movement sleep. However, the presence of physiologically relevant nicotonic receptors has not been described. Intracellular current and single electrode voltage clamp recordings were used to analyse the electrophysiological responses of rat medial pontine reticular formation neurons to nicotinic activation in vitro. In response to the nicotonic agonist, 1,1-dimethyl-4-phenylpiperazinium iodine, depolarization in association with an inward current was observed in 70% of the medial pontine reticular formation neurons. This effect was insensitive to the muscarinic antagonist atropine and the nicotinic ganglionic antagonists mecamylamine and hexamethonium. However, the neuromuscular nicotinic antagonist D-tubocurare and dihydro-beta-erythroidine were effective. This is consistent with a cholinergic activation of medial pontine reticular formation neurons evoking a rapid eye movement sleep-like behavioral state, at least in part, by nicotinic receptors on these neurons.

Animals↗

PubMed1992

4C3HPG (RS-4-carboxy-3-hydroxyphenylglycine), a weak agonist at metabotropic glutamate receptors, occludes the action of trans-ACPD in hippocampus.

The determination of the physiological role of glutamatergic metabotropic actions has been hampered by the lack of potent and specific antagonists. It has recently been reported that 4C3HPG (RS-4-carboxy-3-hydroxyphenylglycine) can antagonize metabotropic responses in the central nervous system. The effects of 4C3HPG on metabotropic responses evoked by trans-ACPD were investigated in CA3 pyramidal cells in hippocampal slice cultures. Our results show that in hippocampus 4C3HPG fails to antagonize responses mediated by metabotropic glutamate receptors.

Animals↗

PubMed1992

Adenosine-mediated synaptic inhibition: partial blockade by barium does not prevent anti-epileptiform activity.

Adenosine-induced inhibition of evoked postsynaptic potentials (PSPs) and epileptiform burst firing in the CA1 subfield of rat hippocampal slices was studied with intracellular recordings in vitro. Adenosine (50 microM) caused a membrane hyperpolarization which was abolished during superfusion with 2 mM Ba2+. The adenosine-induced inhibition of the PSPs was still evident, although the magnitude of the effect was significantly reduced. Adenosine also reduced Ba(2+)-induced burst firing, but less effectively than it did bursts evoked by TEA (5 mM). The results suggest that adenosine inhibits synaptic transmission and epileptiform activity by at least 2 mechanisms: a postsynaptic barium-sensitive increase in gK and a presynaptic effect independent of this adenosine-evoked outward potassium conductance.

Action Potentials↗

PubMed1992

[Iotrolan versus iopamidol. A controlled double-blind study with lumbar myelography].

Within the frame work of lumbar myelography, 158 patients were entered in a double-blind study in order to test a dimeric contrast medium (iotrolan) against a monomeric one (iopamidol), both of them non-ionic. A three-step scheme was applied to evaluate the X-ray pictures with respect to contrast quality. Particular attention was paid to the visibility of details, i.e. the nerve root and its course, as well as to how well it could be distinguished in the nerve root sheath. On the basis of a high level of significance (P less than 0.05), comparison of the two contrast media showed no difference in contrast quality. Sixty-nine percent of the examinations using iotrolan resulted in excellent contrast quality, whereas the corresponding very good results using iopamidol lay at 76%. Twenty-nine percent of the patients examined with iotrolan and 27% of those examined with iopamidol showed side effects. Headache occurred most frequently, followed by nausea, dizziness and neck pain. Sixty percent of the patients suffering from postmyelographic reactions reported delayed headache, which occurred most often with iotrolan rather than iopamidol. As for manifestation of other postmyelographic side effects, there were no significant differences (P less than 0.05, Fischer's test) between the two groups of contrast media.

Adult↗

PubMed1991

Cobalt blocks postsynaptic responses induced by neurotransmitters in the hippocampus in vitro.

Divalent metals such as cobalt are frequently used by neurophysiologists to prevent synaptic transmission, because they are thought to selectively block presynaptic calcium conductance. Recording intracellularly from hippocampal CA3 pyramidal cells we show that Co2+ (2 mM) is not specific in this action but also diminishes postsynaptic responses mediated by agonists acting at ionotropic and metabotropic glutamatergic receptors, as well as GABAA, GABAB, adenosine, and cholinergic receptors. These findings indicate that a more selective substance should be employed for experiments where neurotransmitter release must be blocked.

Animals↗

PubMed1991

Muscarinic agonists activate an inwardly rectifying potassium conductance in medial pontine reticular formation neurons of the rat in vitro.

Intracellular recordings were obtained from neurons in pontine reticular formation slices of the rat to characterize a cholinergic-gated increase in conductance. The conductance increase was associated with a hyperpolarization of the membrane potential and with an outward current under voltage-clamp conditions. Current-voltage relations and potassium substitution experiments indicated mediation by a change in permeability, primarily to potassium. This potassium conductance exhibited inward rectification at membrane potentials negative to resting potential, a novel finding for cholinergic actions in CNS neurons. Further characterization of this inwardly rectifying potassium conductance revealed marked sensitivity to low concentrations of barium. Cholinergically evoked currents were relatively unaffected by the presence of extracellular cesium. Cholinergic effects persisted in TTX. The outward currents elicited by carbachol or methacholine were blocked only by high concentrations of pirenzepine, a selective antagonist of the M1 muscarinic receptor. The interaction between these agents is quantitatively consistent with cholinergic action at postsynaptic muscarinic receptors of the non-M1 subtype.

Animals↗

PubMed1991

Cholinergic fiber growth in co-cultures of CNS tissue.

In co-cultures prepared from the septum and the hippocampus, cholinergic fibers originating in the septal slices grew into the neighboring hippocampal tissue and established functional cholinergic connections with pyramidal cells. To get further insight into the mechanisms governing cholinergic fiber growth, we have added TTX to the growth medium (2 x 10(-7) M) to block propagated electrical activity. Under these conditions, considerably fewer cholinergic cells appeared to survive. A few cholinergic fibers still invaded hippocampal target tissue, but their number was markedly reduced compared with control cultures. Simultaneous application of NGF together with TTX, however, not only increased enzyme levels and enhanced survival of cholinergic neurons, but also led to hippocampal ingrowth in virtually all septo-hippocampal co-cultures. These data, therefore, suggest, that in the absence of spiking activity, cholinergic fibers are capable of growing into a co-cultured target tissue. To test the specificity of growth of septal cholinergic fibers, we have co-cultured septal slices with slices of various brain areas which in situ lack a major cholinergic innervation, in particular the cerebellum. In the vast majority of such co-cultures, cholinergic fibers remained restricted within the septal slices, without innervating cerebellar tissue. This failure might in part be related to the lack of trophic factors released by the target tissue. We have, therefore, grown septo-cerebellar cultures in the presence and absence of NGF. Following application of 100 ng/ml NGF during the entire growth of the cultures, numerous AChE-positive fibers originating in the septal slices invaded the co-cultured cerebellar slices.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Cholinergic activation of medial pontine reticular formation neurons in vitro.

Direct microinjection of cholinergic compounds into pontine reticular formation furnishes an excellent phenomenological model of the rapid eye movement phase of sleep (REM), but the mechanisms underlying this effect and whether they mimic the cellular events of natural REM remain unknown. Data presented here from intracellular recordings in vitro in the rat demonstrate that two-thirds of medial pontine reticular formation neurons respond to application of 0.5-1.0 microM carbachol with a depolarization characterized by a decreased conductance and a linear I/V curve. The resultant mimicry of REM cellular events by carbachol extends to membrane potential depolarization, increased cellular excitability, enhancement of PSPs from reticular stimulation, and the absence of a burst discharge pattern. The presence of these effects with tetrodotoxin and their blockade by atropine imply a direct, muscarinic cholinergic mediation. Other neurons tested responded with either a biphasic hyperpolarization-depolarization or a hyperpolarization. The hyperpolarization was associated with an increased conductance which exhibited pronounced inward rectification, an effect novel for cholinergic agonists in vertebrate CNS but described in heart cells.

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

Repetitive firing properties of medial pontine reticular formation neurones of the rat recorded in vitro.

1. Intracellularly recorded neurones in nucleus reticularis pontis caudalis of the medial pontine reticular formation (mPRF) in the in vitro slice preparation were analysed for repetitive firing properties in response to intracellularly applied constant-current pulses. 2. Three neuronal classes were defined by this procedure: (1) non-burst neurones, which had only a non-burst firing pattern; (2) low-threshold burst neurones, which had either a low-threshold burst pattern or a non-burst pattern; (3) high-threshold burst neurones, which had either a high-threshold burst pattern or a non-burst pattern. 3. Histological characterization of electrophysiologically identified mPRF neurones with carboxyfluorescein showed no definite morphological difference between the first two classes. There was a trend for low-threshold burst neurones to have larger somata. 4. The low-threshold burst was generated by a slow calcium-dependent low-threshold spike, revealed in the presence of tetrodotoxin. The size of the low-threshold spike and thus the number of fast action potentials in the low-threshold burst was controlled by at least five factors including: activation; inactivation; amplitude of low-threshold conductance available to be activated; delayed outward conductance; and early transient outward conductance. 5. The non-burst pattern examined in both non-burst and low-threshold burst neurones appeared to be controlled primarily by one or more calcium-dependent potassium conductances sensitive to the removal of calcium and tetraethyl-ammonium. In the presence of tetrodotoxin (TTX), the addition of antagonists to calcium-dependent potassium current revealed a slow high-threshold calcium spike which was distinguished from the low-threshold spike by its threshold, lack of inactivation (at potentials negative to -40 mV) and insensitivity to Mg2+. A long-duration after-hyperpolarization (greater than 0.5 s) was not observed in any of these cells. 6. An early transient outward rectification sensitive to 4-aminopyridine and probably mediated by A-current was apparent in low-threshold burst and non-burst neurones and affected both the low-threshold burst and non-burst firing patterns. 7. Alteration of resting membrane potential, such as occurs in vivo during the depolarization associated with desynchronized sleep, may inactivate the low-threshold spike and the transient outward conductance responsible for the distinctive responses observed from more hyperpolarized membrane potentials and produce a more homogeneous non-burst response pattern. Membrane potential effects on intrinsic conductances thus may furnish an important mechanism for changes in mPRF neuronal responsivene

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

The effects of beta-adrenergic agonists on cone systems in the cat eye.

The effects of the beta-adrenergic agonist nylidrin and the beta 2-adrenergic agonist clenbuterol on electroretinogram and optic nerve response were studied in the isolated and arterially perfused, light-adapted cat eye. Two cone mechanisms, short wavelength-sensitive and long wavelength-sensitive, were functionally separated by means of intense yellow adaptation. A reversible increase in b-wave amplitude in response to nylidrin or clenbuterol was observed for the cone systems. Both drugs also caused a reversible alteration in configuration of the optic nerve response, mainly a depression of the late components related in time to the changes in the electroretinogram. These observations suggest that beta-adrenergic mechanisms are involved in cone systems. The greater increase in b-wave amplitude on 558-nm stimulation and preliminary evidence for greater increase in sensitivity observed in the V-log I function compared with 439 nm further suggest that the short and long wavelength cone systems are affected differently by beta-adrenergic agonists.

Animals↗

PubMed1988

[Effect of beta-blockers on retinal function in vitro].

In an attempt to identify possible beta-adrenergic mechanisms in the cat retina the authors extended their previous studies on the effects of beta-agonists (Graefe's Arch. clin. exp. Ophthalmol. 225: 33-38, 1987) to three beta-adrenergic antagonists: propranolol, ICI 118.551, and timolol were applied in micromolar concentrations to the arterially perfused, dark-adapted cat eye. The rod ERG b-wave was generally depressed, sometimes enhanced after initial depression (propranolol), without showing any clear-cut dose-dependency. In contrast, the rod-mediated optic nerve action potential exhibited dose-dependent depression of the plateau and OFF components. All effects were reversible within 60-80 minutes. These results, in conjunction with earlier data on the effects of beta-agonists and recent biochemical and autoradiographic studies, strongly support the theory that there are beta-adrenergic synaptic mechanisms located in the inner layers of the mammalian retina.

Adrenergic beta-Antagonists↗

PubMed1987

Effects of beta-agonists on b- and c-waves implicit for adrenergic mechanisms in cat retina.

Nylidrin (buphenine) is a beta-adrenergic agonist known to dilate peripheral vessels and used therapeutically in retinal degeneration and glaucoma. We studied retinal function under beta-agonists in arterially perfused cat eyes and observed a dose-dependent, reversible increase in b-wave amplitude and a decrease in c-wave amplitude in concentrations from 4.5 to 120 microM. A half maximal response was obtained at 40 to 50 microM. The optic nerve response to light showed dose-dependent reversible changes under nylidrin. Standing potential, light peak, intraocular pressure, vascular resistance, and diameter of or retinal vessels showed no consistent changes under nylidrin. The effect were inhibited by each of the beta-blocking agents propranolol, ICI 118, and oxprenolol (in sequence of decreasing potency). Another potent beta 2-agonist, clenbuterol, was used to determine the extent to which the responses to nylidrin were due to beta-receptor-mediated action. Clenbuterol had similar effects on the b-wave and optic nerve response at slightly higher concentrations (30 200 microM) but more variable effects on the c-wave. The data are interpreted as functional evidence that beta-adrenergic mechanisms are involved in retinal signal processing. This concept is corroborated by identification of beta-adrenergic binding sites in cat retina (Bruinink et al., 1986).

Adrenergic beta-Agonists↗