Biomedical subjects

D Bingmann

Publications and source records attributed to D Bingmann.

At least 37 records · Page 2Linked to original sources

PubMed1998

Missing action of carbamazepine on postsynaptic GABA-responses of hippocampal CA3-neurons (slice, guinea pig).

Conflicting data exist concerning the interaction of carbamazepine (CBZ) and GABA-receptors involved in the pathophysiology of neuropsychiatric disorders. The present study reveals that CBZ failed to alter membrane potential fluctuations mediated by an activation of postsynaptic GABA(A)- and GABA(B)-receptors of hippocampal CA3-neurons even at a bath concentration of 500 microM (ca. 10-30 fold the therapeutic level, tested up to 90 min). Therefore, therapeutic effects of CBZ cannot be due to acute modulations of postsynaptic GABA-responses.

Animals↗

PubMed1998

Effects of vitamin D3, 17beta-estradiol, vasoactive intestinal peptide, and glutamate on electric coupling between rat osteoblast-like cells in vitro.

Osteoblast-like cells express receptors for various hormones and neurotransmitters that induce widespread actions in the bone to which intercellular communication and its modulation may contribute. Therefore, we examined the effects of the osteotropic hormones vitamin D3 (vitD3) and 17beta-estradiol (17beta-E2) as well as the neurotransmitter vasoactive intestinal peptide (VIP) and the excitatory amino acid glutamate (Glu) on gap junctions between rat osteoblast-like (ROB) cells in vitro. Electric coupling was measured by simultaneous intracellular recordings from neighboring cells. The coupling factor (cf) was calculated from membrane potential changes induced by alternate current injections into both cells. In ROB cells cf was increased by 5 x 10(-8) mol/L vitD3 to 130 +/- 13% (mean +/- SD; n = 6) of the initial value within 5-20 min. This effect was not reversible after washing with control saline for 10-15 min. In six cell pairs, cf was not affected by vitD3 (94 +/- 5%). In three cell pairs superfusion of 10(-8) mol/L E2 reduced cf to 80 +/- 6% within 10 min, whereas, in two cell pairs, this hormone improved cf to 140% within 20 min. Exposure of VIP (3 x 10(-8) mol/L) did not alter cf in the majority of cells (99 +/- 3%; n = 11). In five cell pairs, cf was improved within 5-15 min to 133 +/- 12%, whereas, in one cell pair, cf was reduced to 22% by VIP. In contrast, brief application of Glu (5 x 10(-3) mol/L) decreased cf to 75 +/- 5% (n = 5), whereas, in nine other cell pairs, cf was not affected (96 +/- 5%). The findings indicate that cell-cell coupling of gap junctions between bone cells can be altered by actions of hormones and transmitters in a cell-pair-specific way, which may depend on their functional state.

Animals↗

PubMed1997

Oxygen consumption of calvarial bone cells in vitro.

Tissues with tortuous and narrow diffusion pathways and cells that are remote from blood vessels nonetheless can show high metabolic activity of which the underlying bases (transport mechanisms) are not fully understood. In one such bone tissue, the O2 consumption was measured by analyzing the decrease in the partial pressure of oxygen (Po2) in a closed chamber containing calvarial fragments from adult guinea pigs (250-400 g) or from neonatal rats and guinea pigs. The O2 consumption of fragments from adult guinea pigs amounted to 0.05, 0.066, and 0.095 ml/100 g* minute at 24, 27, and 36.5 degrees C, respectively. When the temperature exceeded 43 degrees C, O2 consumption irreversibly stopped. Both antimycin A and rotenone, which block the respiratory chain, reduced O2 consumption to approximately 20% of control values. O2 consumption was significantly higher in neonatal animals (0.369 ml/100 g* minute at 27 degrees C) and could be blocked completely by antimycin A. On the basis of the high consumption of O2 by bone cells, we hypothesize that specialized transport systems, i.e., gap junctions, are required to provide a sufficient supply of nutrients to cells in osseous tissue.

Age Factors↗

PubMed1996

Ethacrynic acid: effects on postsynaptic GABA responses and electric activity of CA3 neurones.

Ethacrynic acid (ETA) inhibits somatic Cl(-)-extrusion from hippocampal pyramidal neurones. We analysed the dependence of postsynaptic gamma-aminobutyric acid (GABA) responses on this Cl- extrusion. ETA irreversibly reduced the 'somatic' hyperpolarizing GABAA response (hGABAA) within a few minutes, without altering the following depolarizing GABAA (dGABAA) and hyperpolarizing GABAB responses. GABA-induced changes of the membrane resistance were not affected by ETA, indicating that ETA does not act primarily on receptor-operated channels. In about 50% of the tested CA3 neurones spontaneous activity and caffeine-induced epileptiform discharges increased initially after adding ETA. All neurones lost their activity during prolonged ETA exposure. The early ETA-induced increase of neuronal activity coincided with the decrease of hGABAA (disinhibition). The late suppressive action may be caused by intracellular acidosis.

Animals↗

PubMed1996

Effects of calcium on gap junctions between osteoblast-like cells in culture.

The present study investigated the effects of elevated cytoplasmic free calcium concentrations ([Ca2+]i) on the permeability of gap junctions between cultured osteoblast-like (OB) cells derived from calvarial and periosteal fragments of newborn rats. This was studied using the double whole cell patch clamp technique and intracellular dye injections. To increase [Ca2+]i, patch pipette solutions contained 100 micromol/liter Ca2+. About 1-2 minutes after whole cell modes had been attained, the total number of gap junction channels was reduced from an average of 400 in normal Ca2+ to 20 in high Ca2+. Thereafter, remaining gap junction channels were active for up to 8 minutes. In normal rat kidney (NRK) cells, gap junction channels were closed by high Ca2+ within 1 minute, pointing to a similar sensitivity of Connexin43 gap junction channels in OB and NRK cells. To study the effects of elevated [Ca2+]i on the dye permeability of gap junctions between extended OB cells, the spread of Lucifer Yellow to neighboring cells was evaluated. [Ca2+]i was gradually increased from 1.5- to 14-fold the normal value by application of either ouabain, Na+-free/ouabain, or A23187. Reduced dye spread correlated with the increase of [Ca2+]i measured by analyzing the fluorescence of fura-2. These data show that gap junctions in OB cells are sensitive to Ca2+.

Animals↗

PubMed1996

DAPAS, a computerised workplace for Digital Acquisition and Processing of Analog Signals, with up to two gigabytes data per registration.

A comprehensive and flexible arrangement for Digital long-term Acquisition and Processing of Analog Signals (DAPAS) has been developed. It is especially designed for neurophysiological laboratories and mainly based on IBM-compatible PC components. A/D converters are used, which allow sampling rates of up to 100 kHz (up to 16 bits, 1-16 channels). Signals are stored continuously on DOS devices and on a fast tape streamer, which uses standard video-8 tapes, and which is 2.8 times faster than DAT-based systems. As the recording speed is adapted to the sampling rate, one tape allows recording times of (uncompressed) data acquired at a sampling rate of 100 or 10 kHz of 6.8 and 68 h, respectively. Using a coprocessor-video device, recordings may be scrolled on- or off-line on the screen. In addition, up to eight multi-channel oscilloscopes are displayed simultaneously. DAPAS allows the use of a conventional matrix printer which can act as an inertia-free multi-pen recorder. Defined stored signals are recalled by means of a time code or textual markers. All sections of recordings lasting milliseconds to hours may be displayed within seconds. DAPAS supports export filters for further processing. Thus, this system replaces analog devices (multi-pen recorder, oscilloscope, data recorder), and enables quick, complete digital processing and analysis of neurophysiological data.

Action Potentials↗

PubMed1995

Suppression of rhythmic discharges of medullary neurones in organotypic cultures of new-born rats by calcium antagonists.

The contribution of transmembrane calcium flux to the generation of periodic bioelectric activity in cultured organotypic medullary tissue of 6 day old rats was determined by adding calcium antagonists (CA) to the recording saline and by lowering the calcium concentration of this saline. Organic CA flunarizine and verapamil (50-100 mumol/l) reversibly suppressed rhythmic discharge and diminished the CO2 response of medullary neurones within 30-60 min. Inorganic CA cobalt and magnesium exerted the same effects within a few minutes. After lowering the calcium concentration rhythmic activity became unstable, but recovered on exposure to increased CO2 concentration, the excitatory effect of which was strongly reduced. These findings point to a significant role for transmembrane calcium flux and intracellular calcium concentration in sustaining both periodic activity and the CO2 response of medullary neurones.

Animals↗

PubMed1995

GABAA-responses of CA3 neurones: contribution of bicarbonate and of Cl(-)-extrusion mechanisms.

Postsynaptic GABAA-responses of cortical neurones may be composed of an early 'somatic' hyperpolarization (h-GABAA) and a 'dendritic' depolarization (d-GABAA). In order to study underlying anion-fluxes the gradient of bicarbonate across the membrane of CA3-neurones in hippocampal slices (guinea-pig) was reduced by several manoeuvres (NH4-prepulse-technique, CO2/bicarbonate-withdrawal-technique, acetazolamide, DIDS). Each manoeuvre resulted in an attenuation of d-GABAA. The inhibition of a Cl-/bicarbonate-exchanger with DIDS could also weaken h-GABAA which was selectively impaired by ethacrynic acid--known to block an ATP-driven somatic Cl(-)-extrusion mechanism. In conclusion, bicarbonate-fluxes contribute to d-GABAA rather than to h-GABAA which is mainly driven by Cl(-)-fluxes. An uneven distribution of Cl(-)-extrusion mechanisms along the adult CA3-neurones is likely to build up the anion-gradients necessary to generate biphasic GABAA-responses.

Acetazolamide↗

PubMed1995

Rhythm generation in organotypic medullary cultures of newborn rats.

Organotypic transverse medullary slices (obex level) from six-day-old rats, cultured for two to four weeks in chemically defined medium contained rhythmically discharging neurones which were activated by CO2 and H+. The mechanisms underlying this rhythmicity and the spread of excitation and synaptic transmission within this organotypic tissue were examined by modifying the composition of the external solution. Our findings showed that (1) Exposure to tetrodotoxin (0.2 microM) or to high magnesium (6 mM) and low calcium (0.2 mM) concentrations abolished periodic activity. (2) Neither the blockade of GABAergic potentials with bicuculline methiodide (200 microM) and/or hydroxysaclofen (200 microM) nor the blockade of glycinergic potentials with strychnine hydrochloride (100 microM) abolished rhythmicity. (3) While atropine sulphate (5 microM) was ineffective in modulating periodic discharges nicotine (100 microM) - like CO2-shortened the intervals between the periodic events; hexamethonium (50-100 microM) reduced both periodic and aperiodic activity. (4) Exposure to the NMDA antagonist 2-aminophosphonovaleric acid (50 microM) suppressed periodic events only transiently. In the presence of 2-aminophosphonovaleric acid rhythmicity recovered. However, the AMPA-antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (10-50 microM), abolished periodic activity reversibly within less than 5 min. When 6-cyano-7-nitroquinoxaline-2,3-dione and nicotine were administered simultaneously periodic events persisted for up to 10 min. These findings indicate that synaptic excitatory drive is a prerequisite for the generation of rhythmic discharges of medullary neurones in this preparation. This drive may activate voltage-dependent channels or it may facilitate endogenous cellular mechanisms which initiate oscillations of intracellular calcium concentration. To test the latter possibility (5) calcium antagonists were added to the bath saline. The organic calcium antagonists verapamil and flunarizine (50-100 microM each) and the inorganic calcium antagonists cobalt (2 mM) and magnesium (6 mM) suppressed periodic activity and abolished or weakened the chemosensitivity towards CO2/acidosis. (6) Dantrolene (10 microM). an inhibitor of intracellular calcium release decreased the periodicity, while thapsigargin (2 microM) which blocks endoplasmic Ca(2+)-ATPase, transiently accelerated the occurrence of periodic events. (7) Oscillations of intracellular free calcium concentrations in Fura-2 AM-loaded cells were weakened or abolished by cobalt (2 mM). The results of (5)-(7) indicate that transmembrane calcium fluxes as well as intracellular Ca(2+)-release and -clearance mechanisms are a prerequisite for intracellular free calcium oscillations which may be important in the generation of rhythmic discharges in medullary neurones.

Animals↗

PubMed1995

Effects of carbamazepine on membrane properties of rat sensory spinal ganglion cells in vitro.

The present study aimed to examine effects of the antiepileptic drug carbamazepine (CBZ) on membrane properties. Therefore, effects of CBZ on voltage-dependent ion channels were investigated in rat sensory spinal ganglion cells in primary cultures. (i) Membrane potentials and action potentials were recorded by sharp microelectrodes: CBZ reduced neuronal excitability without changing the resting membrane potential, and suppressed tetrodotoxin (TTX)-resistant components of action potentials which were blocked by cobalt and hence were interpreted as Ca2+ spikes. The rising phase and peak amplitude of TTX-sensitive components of action potentials, however, were hardly altered. (ii) Voltage-dependent inward and outward currents were elicited in the whole-cell configuration of the patch clamp technique. CBZ reduced (presumably L-type) Ca2+ currents. In some cells Ca2+ currents partly recovered during washing with control saline. The effects on Na+ and K+ currents were not uniform and often insignificant. The present study indicates that CBZ has calcium-antagonistic properties.

Action Potentials↗

PubMed1994

Epileptogenic actions of xanthines in relation to their affinities for adenosine A1 receptors in CA3 neurons of hippocampal slices (guinea pig).

In order to analyze the epileptogenic mechanisms of caffeine and related xanthines, putative effects of these drugs were studied on adenosine receptors of CA3 neurons in hippocampal slices. Epileptogenic concentrations of different xanthine derivatives strongly correlated with their affinities for the inhibitory A1 adenosine receptor subtype. The A1 receptor agonists adenosine and R-PIA reversibly depressed xanthine-induced epileptic activity without effects on the resting membrane potential or on spontaneously occurring action potentials. These findings suggest that the epileptogenic potency of xanthines is primarily due to the blockade of the A1 receptors through an abnormal rise of intracellular cAMP and to the excessive transmembrane calcium fluxes underlying paroxysmal depolarization shifts.

Adenosine↗

PubMed1993

Dye and electric coupling between osteoblast-like cells in culture.

Primary cultures of osteoblast-like cells (OB) derived from calvarial fragments of newborn rats and juvenile guinea pigs formed numerous gap junctions between neighboring cells in vitro. Intracellular injection of Lucifer yellow led to a staining of up to 30 adjacent cells. Parallel intracellular recordings showed that amplitudes of stimulated membrane potential changes (4-5 mV) were closely related between coupled cells. The coupling factor, which was derived from the ratio of these amplitudes, ranged between 0.1 and 0.8. The coupling factor (1) was not dependent on the membrane potential or the injected current strength; (2) strong acidosis (pH < 6.6) and hypercapnia (pCO2 > 80 mm Hg) did not affect electric or dye coupling; (3) elevation of intracellular cAMP level was ineffective; (4) rise of the extra- and intracellular Ca2+ concentration did not effect the electric coupling; (5) the anticonvulsant drugs carbamazepine and phenytoin impaired the coupling factor up to 59%. The findings show that cell-cell communication between OB via gap junctions proved stable under various conditions which, in other tissues, were found to reduce the coupling strength of gap junctions.

1-Octanol↗

PubMed1993

Morphology of CA3 neurons in hippocampal slices with nonepileptic and epileptic activity: a light and electron microscopic study.

In guinea pig hippocampal slices, relations between morphology and spontaneous bioelectric activity of neurons were studied in control saline and with exposure to the epileptogenic drug pentylenetetrazole (PTZ) for 2-3 h. Light and electron microscopic structures of the CA3 region were analysed after recording the membrane potential. Neurons in slices kept in control saline exhibited spontaneous aperiodic bioelectric activities partly mixed with rhythmically occurring burst discharges. In slices exposed to PTZ, these periodic burst discharges and/or paroxysmal depolarization shifts (PDS) predominated. Light microscopic comparison focussing on tissue preservation showed no significant differences between control and PTZ-treated slices. Ultrastructural morphology revealed, on the one hand, no differences regarding spine and synaptic densities, and on the other hand, significantly more irregular electron translucent vacuoles within dendrites of PTZ-treated slices being either randomly distributed or clustered. The vacuoles are interpreted as early changes during epileptic activity.

Animals↗

PubMed1993

GABA-responses of CA3 neurones at epileptogenic threshold concentrations of convulsants.

Epileptogenic actions of convulsants are often attributed to weakened inhibitory synaptic mechanisms. This assumption was tested by studying GABA-induced postsynaptic membrane potential (MP) changes of CA3 neurones (guinea-pig) before and during exposure to bicuculline methoiodide (BMI), pentylenetetrazol (PTZ), penicillin (PEN) and caffeine (CAF). Under control conditions GABA ejections elicited polyphasic MP fluctuations (components I-III). After adding BMI, PTZ, PEN or CAF, early hyperpolarizations (component I) did not change at epileptogenic threshold concentrations. These convulsants, however, exerted differential effects on the depolarizing component II, but only threshold concentrations of penicillin strongly reduced the amplitude of this component. Simultaneously, component III was slightly accentuated. These findings indicate that changes of GABA responses are not an essential prerequisite for the generation of paroxysmal depolarizations.

Action Potentials↗

PubMed1993

Calcium-antagonistic effects of carbamazepine in epilepsies and affective psychoses.

Carbamazepine (CBZ) is known to have beneficial effects in the treatment of epilepsies and in the prophylaxis of affective disorders. Since increased transmembrane calcium fluxes and intracellular calcium concentrations play a key role in the generation of epilepsies and possibly also in the development of these psychiatric disorders the effects of CBZ on epileptic discharges (elicited by caffeine, penicillin and low Mg2+) in CA3 neurons of hippocampal slices were compared with those of the organic calcium antagonist verapamil and found to be almost the same.

Animals↗

PubMed1993

Effects of carbamazepine on action potentials and calcium currents in rat spinal ganglion cells in vitro.

The effects of carbamazepine (CBZ) on action potentials and calcium currents in cultured rat sensory spinal ganglion cells were investigated. CBZ was found to reversibly suppress the calcium-dependent components of action potentials and to reduce the amplitude of the after-hyperpolarizations, while the rising phase and the peak amplitude were hardly changed. Furthermore, CBZ caused a marked reduction in the calcium currents, which in some cells was reversible. The present findings confirm that CBZ has calcium-antagonistic properties.

Action Potentials↗

PubMed1992

Characterization of gap junctions between osteoblast-like cells in culture.

The structure of gap junctions in osteoblast-like cells (OBs) and the connexins (cx) that build up these structures were characterized by ultrastructural, immunocytochemical, and molecular techniques. Ultrastructural studies revealed numerous gap junctions which were mostly located on processes of neighboring cells. Immunofluorescence labeling using two different antibodies (specific to mouse live cx26 and cx32 and to a peptide-specific rat heart gap junction protein cx43) gave evidence that in OBs, gap junctions consist mainly of cx43. The presence of cx43 in cultured OB was also confirmed by Western blot analysis. Dye-coupling with Lucifer yellow led to a staining of up to 30 neighboring cells. Parallel intracellular recordings showed that membrane potential amplitude changes (4-5 mV) are typically related to those in the coupled cells. Thus, there is morphological and functional evidence for intercellular communication between OB in culture. OBs in culture express the same connexins as observed in vivo and may serve as a model to investigate electrophysiological events in response to different stimulation signals.

Animals↗

PubMed1992

Calcium antagonistic effects of carbamazepine as a mechanism of action in neuropsychiatric disorders: studies in calcium dependent model epilepsies.

Carbamazepine (CBZ) is used in neurology for the treatment of epilepsies and trigeminal neuralgia and in psychiatry for the prophylactic treatment of affective and schizoaffective psychoses. Since a common mechanism of epilepsies and affective psychoses might be increased intracellular calcium ion levels, CBZ action was analyzed in penicillin, caffeine and low Mg2+ induced model epilepsies which have been shown to be suppressed specifically by organic calcium antagonists. In CA3 and CA1 areas of hippocampal slice preparations of guinea pigs CBZ reduced paroxysmal depolarizations and extracellular field potentials (EFP) in a typical time and concentration dependent manner as it is known from calcium antagonists. Furthermore, subthreshold concentrations of the organic calcium antagonist verapamil intensified the action of CBZ. NMDA induced increases of the discharge rate of EFP were, however, unaffected by CBZ.

Animals↗