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B Antkowiak

Publications and source records attributed to B Antkowiak.

18 recordsLinked to original sources
PubMed2006

Effects of isoflurane and enflurane on GABAA and glycine receptors contribute equally to depressant actions on spinal ventral horn neurones in rats.

BACKGROUND: Volatile anaesthetics are widely used agents in clinical anaesthesia, although their mechanism of action is poorly understood. In particular, the dominant molecular mechanisms by which volatile anaesthetics depress spinal neurones and thereby mediate spinal effects such as immobility have recently become a matter of dispute. As GABAA and glycine receptors are potential candidates we investigated the impact of both receptor systems in mediating the depressant effects of isoflurane and enflurane on spinal neurones in rats. METHODS: The effects of isoflurane and enflurane on spontaneous action potential firing were investigated by extracellular voltage recordings from ventral horn interneurones in cultured spinal cord tissue slices obtained from embryonic rats (E 14-15). RESULTS: Isoflurane and enflurane reduced spontaneous action potential firing. Concentrations causing half-maximal effects (isoflurane: 0.17 mM; enflurane: 0.50 mM) were less than EC50-immobility (isoflurane: 0.32 mM; enflurane: 0.62 mM). Effects of isoflurane were mediated by 39% by glycine receptors and 36% by GABAA receptors. The effects of enflurane were mediated 26% by GABAA receptors and 29% by glycine receptors. CONCLUSION: These results demonstrate that the effects of isoflurane and enflurane on GABAA and glycine receptors contribute almost equally to their depressant actions on spinal ventral horn neurones in rats. The fraction of inhibition mediated by both receptor systems differs between specific volatile anaesthetics. Our data argue against the theory that a dominant molecular mechanism accounts for spinal effects of volatile anaesthetics.

Action Potentials↗
PubMed2006

[The GABA(A) receptor family: possibilities for the development of better anesthetics].

Clinically used anesthetics show amnestic, sedative, hypnotic and immobilizing properties. On a molecular level these drugs affect several receptors in the cell membrane of neurons. By using genetically engineered mice a linkage can now be made between actions on certain receptors and clinically desired and undesired effects. Experiments show that a certain GABA(A) receptor subtype mediates hypnosis and immobility, whereas another subtype is involved in side-effects like sedation and hypothermia. These findings form the basis for the development of new drugs, acting highly specific and with fewer side-effects.

Anesthetics↗
PubMed2001

How do general anaesthetics work?

Almost a century ago, Meyer and Overton discovered a linear relationship between the potency of anaesthetic agents to induce general anaesthesia and their ability to accumulate in olive oil. Similar correlations between anaesthetic potency and lipid solubility were later reported from investigations on various experimental model systems. However, exceptions to the Meyer-Overton correlation exist in all these systems, indicating that lipid solubility is an important, but not the sole determinant of anaesthetic action. In the mammalian central nervous system, most general anaesthetics act at multiple molecular sites. It seems likely that not all of these effects are involved in anaesthesia. GABAA- and NMDA-receptor/ion channels have already been identified as relevant targets. However, further mechanisms, such as a blockade of Na+ channels and an activation of K+ channels, also come into play. A comparison of different anaesthetics seems to show that each compound has its own spectrum of molecular actions and thus shows specific, fingerprint-like effects on different levels of neuronal activity. This may explain why there is no known compound that specifically antagonises general anaesthesia. General anaesthesia is a multidimensional phenomenon. Unconsciousness, amnesia, analgesia, loss of sensory processing and the depression of spinal motor reflexes are important components. It was not realised until very recently that different molecular mechanisms might underlie these different components. These findings challenge traditional views, such as the assumption that one anaesthetic can be freely replaced by another.

Anesthesia, General↗
PubMed2000

[Neural mechanisms of anesthesia].

Positron emission tomography studies on volunteers showed that, at concentrations inducing the loss of consciousness, propofol, halothane and isoflurane reduce glucose metabolism of neocortical neurones by 20-50%. To find out whether these effects are caused by direct anaesthetic actions on cortical structures, experiments were carried out on isolated neocortical brain slices. In these investigations an excellent correlation was observed between anaesthetic concentrations causing a half-maximal depression of action potential firing in neocortical brain slices and anaesthetic blood concentrations monitored during awaking from anaesthesia in humans. Furthermore, it could be shown that, at concentrations approximately one half the MAC-value, isoflurane decreases the frequency of auditory evoked 30-40 Hz oscillations in the neocortex by 50%. Similar quantitative effects were observed on spontaneously occurring high frequency rhythms in neocortical brain slices. However, not all aspects of cerebral anaesthetic actions can be explained by direct effects on cortical neurones. The EEG synchronisation and the amplitude reduction of mid latency auditory evoked potentials are probably related to the inhibition of thalamic neurones. Halothane, isoflurane, enflurane and propofol reduced action potential firing of cortical neurones by enhancing GABAA receptor-mediated synaptic inhibition. This molecular mechanism seems also to be involved in depressing painful stimuli-induced motor responses. Nevertheless, there must be a difference between relevant anaesthetic mechanisms on the cerebral and spinal level. This follows from the observation that the relation between the concentration causing the loss of consciousness and the concentration that depresses movements considerably varies among different anaesthetic agents.

Anesthetics↗
PubMed1999

NMDA receptor-mediated changes of spontaneous activity patterns in thalamocortical slice cultures.

Spontaneous activity is a hallmark of the thalamocortical system in vivo. Up until now, in vitro preparations of this system have been shown to be spontaneously active only when inhibition was reduced or N-methyl-D-aspartate (NMDA) receptor-mediated currents were facilitated via low extracellular magnesium levels. This study investigated the dependence of spontaneous thalamocortical activity patterns on NMDA receptor function via variation of extracellular magnesium levels (0-1 mM) and by the application of the specific NMDA receptor-antagonist D-2-amino-5-phosphonovalerate (AP5) in the absence of magnesium. We used cocultures of rat neocortical and thalamic slices which have been shown to develop reciprocal synaptic connections similar to those in vivo. Multi-site extracellular recordings revealed that the cultures were spontaneously active at all concentrations of magnesium and AP5, albeit with a high variability among cultures. Activity consisted of burst-like events which were largely synchronized within as well as among the neural tissues, and thalamic background activity during periods of neocortical quiescence. Each tissue was capable of triggering activity in the other, indicating that both thalamocortical and corticothalamic synaptic connections were functional. With increasing magnesium concentration, activity rates declined in both tissues and the site of origin of the synchronous, burst-like events shifted from neocortex to thalamus. AP5 in magnesium-free perfusion solution had qualitatively similar effects. We conclude that thalamic activity is not as dependent on the facilitation of NMDA receptor-mediated currents as neocortical activity and consequently, that the thalamus is the pacemaker of thalamocortical synchronized activity in physiological in vitro conditions.

2-Amino-5-phosphonovalerate↗
PubMed1999

Different actions of general anesthetics on the firing patterns of neocortical neurons mediated by the GABA(A) receptor.

BACKGROUND: In cultured slice preparations of rat neocortical tissue, clinically relevant concentrations of volatile anesthetics mainly decreased action potential firing of neurons by enhancing gamma-aminobutyric acid (GABA(A)) receptor-mediated synaptic inhibition. The author's aim was to determine if other anesthetic agents are similarly effective in this model system and act via the same molecular mechanism. METHODS: The actions of various general anesthetics on the firing patterns of neocortical neurons were investigated by extracellular single-unit recordings. RESULTS: Pentobarbital, propofol, ketamine, and ethanol inhibited spontaneous action potential firing in a concentration-dependent manner. The estimated median effective concentration (EC50) values were close to or below the EC50 values for general anesthesia. Bath application of the GABA(A) antagonist bicuculline (100 microM) decreased the effectiveness of propofol, ethanol, halothane, isoflurane, enflurane, and diazepam by more than 90%, indicating that these agents acted predominantly via the GABA(A) receptor. The depressant effects of pentobarbital and ketamine were not significantly reduced by bicuculline treatment. Drugs acting mainly via the GABA(A) receptor altered the firing patterns of neocortical cells in different manners. Diazepam reduced the discharge rates by decreasing the number of action potentials per burst, leaving the burst rate unaffected. In contrast, muscimol, GABA, propofol, and volatile anesthetics decreased the burst rate. CONCLUSIONS: Although several anesthetic agents acted nearly exclusively via the GABA(A) receptor, they changed the discharge patterns of cortical neurons in different ways. This finding is explained by GABA-mimetic or benzodiazepine-like molecular interactions.

Action Potentials↗
PubMed1998

Effects of small concentrations of volatile anesthetics on action potential firing of neocortical neurons in vitro.

BACKGROUND: Volatile general anesthetics depress neuronal activity in the mammalian central nervous system and enhance inhibitory Cl- currents flowing across the gamma-aminobutyric acid A (GABA(A)) receptor-ion channel complex. The extent to which an increase in GABA(A)-mediated synaptic inhibition contributes to the decrease in neuronal firing must be determined, because many further effects of these agents have been reported on the molecular level. METHODS: The actions of halothane, isoflurane, and enflurane on the firing patterns of single neurons were investigated by extracellular recordings in organotypic slice cultures derived from the rat neocortex. RESULTS: Volatile anesthetics depressed spontaneous action potential firing of neocortical neurons in a concentration-dependent manner. The estimated median effective concentration (EC50) values were about one half the EC50 values for general anesthesia. In the presence of the GABA(A) antagonist bicuculline (20 microM), the effectiveness of halothane, isoflurane, and enflurane in reducing the discharge rates were diminished by 48-65%, indicating that these drugs act via the GABA(A) receptor. CONCLUSIONS: Together with recent investigations, our results provide evidence that halothane, isoflurane, and enflurane reduced spontaneous action potential firing of neocortical neurons in cultured brain slices mainly by increasing GABA(A)-mediated synaptic inhibition. At concentrations, approximately one half the EC50 for general anesthesia, volatile anesthetics increased overall GABA(A)-mediated synaptic inhibition about twofold, thus decreasing spontaneous action potential firing by half.

2-Amino-5-phosphonovalerate↗
PubMed1998

Ultradian rhythms in Desmodium.

The leaves of Desmodium gyrans (L.F.) DC show circadian movements in the terminal and ultradian movements of the lateral leaflets. The movements are due to swelling and shrinking of motor cells in special organs. The anatomy of these pulvini is described for the lateral leaflets. Data from electrophysiological recordings using microelectrodes inserted into the lateral pulvini, together with treatments that affect the proton pumps and ion channels, have been used to develop a physiological model of the ultradian leaflet movement. It explains the oscillations in the motor cells as being due to a change between a pump state and depolarization. During the pump state, ions are taken up, causing water influx and swelling of the motor cells. Depolarization causes loss of ions and water efflux (the motor cells shrink). The roles of calcium and the phosphatidyl inositol signal chain are discussed on the basis of experiments using chemical agents that affect these processes. Since calcium oscillations are known to occur in organisms in both time and space, an attempt has been made to simulate the situation in Desmodium pulvini by a model of specially coupled oscillators. Effects of different other treatments of the lateral pulvini are discussed. Oscillations in the minute range seem to be more common and some might be related to turgor regulation and ion uptake comparable to the situation in Desmodium. The ultradian control of the lateral pulvini and the circadian control of the terminal pulvini are apparently based on different mechanisms.

Activity Cycles↗
PubMed1997

Effects of volatile anaesthetics on the membrane potential and ion channels of cultured neocortical astrocytes.

Volatile anaesthetics cause changes in the membrane resting potential of central neurons. This effect probably arises from actions on neuronal ion channels, but may also involve alterations in the ion composition of the extracellular space. Since glial cells play a key role in regulating the extracellular ion composition in the brains of mammals, we analyzed the effects of halothane, isoflurane and enflurane on the membrane conductances and ion channels of cultured cortical astrocytes. Astrocytes were dissociated from the neocortex of 0-2-day old rats and grown in culture for 3-4 weeks. Anaesthetic-induced changes in the membrane potential were recorded in the whole cell current-clamp configuration of the patch-clamp technique. We further studied the effects of halothane and enflurane on single ion channels in excised membrane patches. At concentrations corresponding to 1-2 MAC (1 MAC induces general anaesthesia in 50% of the patients and rats), membrane potentials recorded in the presence of enflurane, isoflurane and halothane did not differ significantly from the control values. At higher concentrations, effects of enflurane and halothane, but not of isoflurane, were statistically significant. Single-channel recordings revealed that halothane and enflurane activated a high conductance anion channel, which possibly mediated the effects observed during whole cell recordings. In less than 10% of the membrane patches, volatile anaesthetics either increased or decreased the mean open time of K+-selective ion channels without altering single-channel conductances. In summary, it seems unlikely that the actions of volatile anaesthetics described here are involved in the state of general anaesthesia. Statistically significant effects occurred at concentrations ten times higher than those required to cause half-maximal depression of action potential firing of neocortical neurons in cultured brain slices. However, it cannot be excluded that the changes observed in the membrane conductance of cortical astrocytes disturb the physiological function of these cells, thereby influencing the membrane resting potential of neurons.

Anesthetics, Inhalation↗
PubMed1997

Cellular mechanisms of gamma rhythms in rat neocortical brain slices probed by the volatile anaesthetic isoflurane.

In hippocampus slice preparations, the frequency of gamma oscillations (30-80 Hz) is inversely related to the decay time of GABA(A)-mediated inhibitory postsynaptic currents (IPSCs), suggesting a causal relationship [Jefferys, J.R.G., Traub, R.D. and Whittington, M.A., Neuronal networks for induced '40 Hz' rhythms, Trends Neurosci., 19 (1996) 202-207]. We determined the effects of the commonly used volatile anaesthetic isoflurane on IPSCs monitored from neocortical and cerebellar neurons, as well as on gamma oscillations detected in the field potential of neocortical brain slices. At 0.16 mM, the anaesthetic lengthened IPSC-decays by a factor of 1.7 and decreased the frequency of gamma oscillations by 41%. Quantitatively equivalent effects of isoflurane on gamma rhythms were discovered during encephalographic recordings from human patients [Munglani, R., Andrade, J., Sapsford, D.J., Baddeley, A. and Jones, J.G., Br. J. Anaesth., 71 (1993) 633-641].

Anesthetics, Inhalation↗
PubMed1997

Effects of volatile anaesthetics on spontaneous action potential firing of cerebellar Purkinje cells in vitro do not follow the Meyer-Overton rule.

We have investigated in rat brain slices the effects of the volatile anaesthetics enflurane, isoflurane and halothane on spontaneous discharge patterns and mean firing rates of cerebellar Purkinje cells. In the absence of these anaesthetics, Purkinje cells fired bursts of action potentials separated by quiescent periods lasting less than 2 s. Mean discharge rates were 10.8 (SEM 0.4) Hz at 23 +/- 1 degrees C and 25.6 (1.2) Hz at 35 +/- 1 degrees C. The agents exhibited qualitatively different effects when applied at concentrations corresponding to 1-3 MAC. Enflurane markedly lengthened burst and inter-burst durations. Isoflurane acted in a similar manner, but effects were less pronounced. In contrast with isoflurane and enflurane, halothane shortened burst durations. At concentrations corresponding to 1-1.5 MAC, halothane, isoflurane and enflurane significantly depressed action potential firing by 15-30% (P < 0.05). Enflurane 1.2 mmol litre-1 (2.0 MAC), isoflurane 0.9 mmol litre-1 (2.8 MAC) and halothane 0.9 mmol litre-1 (3.8 MAC) depressed spontaneous spike rates by 50%. The changes in discharge patterns and the concentration-dependent decrease in the firing rates were similar at 23 +/- 1 degrees C and 35 +/- 1 degrees C. In summary, we observed that neither the anaesthetic-induced alterations in spontaneous discharge patterns nor the EC50 values of the concentration-dependent depression of the mean firing rates were in accordance with the Meyer-Overton rule. However, at clinically relevant concentrations, depression of average spike rates did not differ significantly between the anaesthetics and thus followed the rule. Our results suggest that anaesthetic actions, which are in accordance with the rule, are frequently masked by several side effects.

Action Potentials↗
PubMed1997

Effects of the volatile anesthetic enflurane on spontaneous discharge rate and GABA(A)-mediated inhibition of Purkinje cells in rat cerebellar slices.

The effects of the volatile anesthetic enflurane on the spontaneous action potential firing and on gamma-aminobutyric acid-A (GABA(A))-mediated synaptic inhibition of Purkinje cells were investigated in sagittal cerebellar slices. The anesthetic shifted the discharge patterns from continuous spiking toward burst firing and decreased the frequency of extracellularly recorded spontaneous action potentials in a concentration-dependent manner. Half-maximal reduction was observed at a concentration corresponding to 2 MAC (1 MAC induces general anesthesia in 50% of patients and rats). When the GABA(A) antagonist bicuculline was present, 2 MAC enflurane reduced action potential firing only by 13 +/- 8% (mean +/- SE). In further experiments, inhibitory postsynaptic currents (IPSCs) were monitored in the whole cell patch-clamp configuration from cells voltage clamped close to -80 mV. At 1 MAC, enflurane attenuated the mean amplitude of IPSCs by 54 +/- 3% while simultaneously prolonging the time courses of monoexponential current decays by 413 +/- 69%. These effects were similar when presynaptic action potentials were suppressed by 1 microM tetrodotoxin. At 1-2 MAC, enflurane increased GABA(A)-mediated inhibition of Purkinje cells by 97 +/- 20% to 159 +/- 38%. During current-clamp recordings, the anesthetic (2 MAC) hyperpolarized the membrane potential by 5.2 +/- 1.1 mV in the absence, but only by 1.6 +/- 1.2 mV in the presence, of bicuculline. These results suggest that enflurane-induced membrane hyperpolarizations, as well as the reduction of spike rates, were partly caused by an increase in synaptic inhibition. Induction of burst firing was related to other actions of the anesthetic, probably an accelerated activation of an inwardly directed cationic current and a depression of spike afterhyperpolarizations.

Action Potentials↗
PubMed1994

Systems analysis of yeast glycolysis using perturbations of external pH: physiological parameters, non-parametric analysis, and general properties of the system dynamics.

A global systems analysis approach to yeast glycolysis is presented. Starting from a high flux steady state of anaerobic glycolysis rapid changes of external pH are applied. The dynamics of the transduction of the pH signal to the in vivo fluorescence of reduced pyridine nucleotides are investigated. Physiological studies indicate no significant influence of external pH on glycolytic flux and energy charge, but stationary concentrations of metabolites are increased after increasing the external pH from 5-7 particularly in the distal part of the glycolytic chain. Most of the changes in reduced pyridine fluorescence are due to glycolytically accessible NADH. As a first stage of system analytic investigations the premises for the approach were tested. The dynamic properties of the system are stable and the response is linear with respect to the input amplitude. The dynamic properties of the system depend on the state of adaptation to a certain external pH. The non-parametric model derived from single step experiments was used to correctly predict the response to pulses of variable duration. This indicates that the linear macroscopic approach to systems analysis with pH as input is applicable. The dynamics of the system response includes strongly damped oscillatory components. Their period lengths are similar to those found with temperature inputs and with the switching from low to high glycolytic flux under anaerobic conditions. This indicates that the three different signals may trigger common regulatory interactions. The order of the signal transduction process, indicating the number of basic processes involved, can be estimated to be 4 or higher.

Glycolysis↗
PubMed1992

Enflurane is a potent inhibitor of high conductance Ca(2+)-activated K+ channels of Chara australis.

The volatile anaesthetic, enflurane, is commonly used in surgery for inducing the state of general anaesthesia. It is assumed, that general anaesthetics act on ion channels, but little is known of how they do so and what kinds of channels are sensitive. We found, that enflurane inhibits a large conductance Ca(2+)-activated K+ channel of the green alga, Chara australis. Effects occur at clinically relevant concentrations are fully reversible. The actions of enflurane are distinct from those of charybdotoxin and tetraethylammonium, which are well known blockers of this channel type. Kinetic analysis of single-channel data demonstrates multiple effects of enflurane on the channel protein.

Calcium↗
PubMedDate not supplied

Psychosomatic reactions to a stressful environment and an attempt at pharmacological modification.

BACKGROUND: Extreme environmental conditions significantly influence the functioning of the human organism and trigger distinct stress reactions. In our study we attempted to create an experimental model of complex stress conditions. MATERIAL AND METHODS: Healthy male volunteers were isolated, deprived of food and sleep, and exposed to extreme temperatures for 5 consecutive days. Physical fitness and selected somatic parameters and biochemical stress markers were measured in the tested subjects. In addition, changes in behavior and mental status were assessed by means of a set of psychological tests. Finally, the effects of pharmacological modification (administration of clobazam and tramadol) on psychosomatic stress reactions were tested. CONCLUSIONS: The results indicate that our experimental stress conditions slightly altered the mental functions of the subjects, increased their anxiety level, hampered their physical efficiency, and led to weight loss. The administration of the drugs beneficially influenced the subjects' memory and physical efficiency.

Adrenal Cortex Hormones↗