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S Stolc

Publications and source records attributed to S Stolc.

53 records · Page 3Linked to original sources
PubMed1988

Potential clamp of isolated dialyzed neuron: minimalization of the effect of series resistance.

A modification of the technique of intracellular dialysis of isolated single excitable cells, such as rat spinal ganglion neuron, suitable for potential clamping of its somatic membrane is described. The advantage of the new modification is the substantial reduction of the effect of inherent resistance in series (RS) to the membrane resistance (RM) on precision of potential clamping. This is attained by reversal of cell position in the perfusion pipette resulting in an approximately tenfold reduction in the area of active membrane. The resistance of this area proportionally increased while RS remained unchanged. Hence the error in potential fixation, which is inversely proportional to the ratio RM/RS, is by approximately one order smaller with the new technique than with the original one. An essential step in the new technique is the osmotic expansion of the cell to improve the contact of the cell with the perfusion pipette in the pore and to facilitate disruption of the appropriate part of the membrane. All features and advantages of the technique of intracellular dialysis, such as simplicity, the possibility to easily change ionic composition of media, and/or to apply drugs to any side of the membrane in the same cell, etc., have been maintained.

Cell Membrane↗
PubMed1987

pH-dependent effects of local anaesthetics in perturbing lipid membranes.

The effects of local anaesthetics lidocaine, benzocaine, carbisocaine and carbisocaine derivatives, KaQ-7 and Ka-O, in perturbing bovine brain lipid membranes or egg lecithin membranes were compared at pH 6.0; 7.0; and 8.0. The electron spin resonance method with stearic acid labeled at carbon position 16 as the spin probe was employed. The perturbation effects of lidocaine and Ka-O were found to increase with increasing pH of the sample, whereas the effect of carbisocaine decreased with increasing pH. The perturbation effects of benzocaine and KaQ-7 were independent of pH. The pH-dependent perturbation effects of the local anaesthetics tested on lipid membrane fairly corresponded with their pH-dependent potency to block nerve action potentials.

Anesthetics, Local↗
PubMed1986

Perturbation of lipid membranes by local anaesthetic carbisocaine.

Local anaesthetic carbisocaine decreased the electrical conductivity of gramicidin channels in planar lipid membrane made from bovine brain total lipids in n-hexane at the concentration (1.6 +/- 1.3) X 10(-5) mol/l, which is similar to that found to block propagation of action potential on the sciatic nerve. To study the mechanism of this effect the authors investigated the disordering effect of carbisocaine on rat total lipid membranes at the 5th, 12th and the 16th carbon membrane depths, using ESR spectroscopy of spin-labelled stearic acids. Carbisocaine disorders the membrane and the effect increases towards the methyl terminal of the lipid acyl chains. It is suggested that carbisocaine-induced perturbation of the membrane may have a secondary influence on the conductivity of gramicidin channels in the membrane.

Anesthetics, Local↗
PubMed1986

A pH-dependent disordering efficacy of new local anaesthetics with carbanilate structure. A spin label study in model membranes.

Electrophysiological investigations of new drugs with carbanilate structure (heptacaine, carbisocaine) on axons and sciatic nerves of the rat have shown their high local anaesthetic effect at physiological pH. This effect is not only maintained at acid pH (6.0); it even increases on shifting pH from basic to acid values. To study this unique pH dependence of the effect of new local anaesthetics, drug-lipid interactions were investigated in liposomes prepared from egg yolk phosphatidylcholine or dimyristoyl phosphatidylcholine. The effect of the local anaesthetics on the molecular ordering of lipids in the liposomes was measured from spectral anisotropy of spin-labelled fatty acid incorporated in the membrane. It was concluded that the change of pH from 9.5 to 6.5 not only sustains the disordering effect of heptacaine and carbisocaine; it even potentiates it with the maximum disordering effect recorded at pH 6.5. This trend towards pH dependence in the effect of the new local anaesthetics is similar to that observed in biological preparations and is quite unlike the case of classic local anaesthetics (procaine, lidocaine). The possible mechanism of pH dependence is discussed.

Anesthetics, Local↗
PubMed1986

Effect of local anaesthetics and pH: new aspects.

The pH dependence of the effect of local anaesthetics with ester, amide, or carbanilate structure on action potential conduction was studied in rat desheathed sciatic nerve and in single axon preparation in vitro. Not only different slopes but also different directions of this dependence were observed in the pH range 6.0-8.4. The effect of common local anaesthetics such as procaine, lidocaine, trimecaine, and bupivacaine kept decreasing with lower pH. New drugs with carbanilate structure, however (pentacaine, carbisocaine and heptacaine) displayed an opposite dependence. Further analysis showed that this phenomenon cannot be linked to the type of the intermediary chain of the drugs, to differences in pKa values, or to differences in potency of the drugs. Yet a relationship was found to exist between pH dependence and the lipophilicity of the drug. It is suggested that the current hypothesis concerning the pH dependence of the effect of local anaesthetics be complemented by the lipophilic properties of such drugs. This implies a pH dependent formation of micelles in highly lipophilic local anaesthetics which changes their bioavailability, as well as a diffusion of these drugs into and through the lipoid phase besides the base also in the form of an ion pair.

Action Potentials↗
PubMed1986

pH dependence of the blocking activity of carbisocaine and its derivatives.

The blocking activity and pH dependence of carbanilate local anaesthetics, carbisocaine and its homologues, were tested on isolated rat sciatic nerves at pH 6.0, 7.2 and 8.4. Carbisocaine blocked the compound action potential more strongly than the derivatives with shorter alkoxysubstituents. The blocking potency of shorter derivatives increased with the rise of external medium pH, whereas the activity of carbisocaine increased with decreasing external pH. Quaternary compounds applied in the external medium were able to block the action potential, but in higher concentrations and with a longer half-time than their tertiary analogues. The blocking potency of quaternary derivatives correlated well with the length of the alkoxysubstituent and thus also with their lipophilicity. Extracellular pH did not consistently change the inhibitory effect of quaternized derivatives. These observations support the view that the lipophilicity of local anaesthetics is one of the possible factors determining their anaesthetic activity and the pH dependence of their effect.

Action Potentials↗
PubMed1984

Perturbation effect of local anaesthetics on synaptosomes: variation with depth of the spin label probe.

Stearic acids labeled with a doxyl group at the 5th, 12th and 16th carbon positions were used as the spin probes for an investigation of the perturbation effects of two local anaesthetics (the 2-piperidinoethylester of phenyl carbamic acid and the piperidinoethylester of 2-heptyloxyphenylcarbamic acid) on rat brain synaptosomes. For a quantitation of the perturbation effects we have studied the order parameter S of the spin probe, incorporated in the membrane, calculated from the ESR spectra as a function of temperature and concentration of local anaesthetics. The local anaesthetics had a different disordering efficiency at different depths of the membrane. It follows from our results that the perturbing effects of the anaesthetics increase relative to the depth of the membrane, and the extent of perturbation correlates with local anaesthetic activity.

Anesthetics, Local↗
PubMed1984

Effects of tertiary amine local anaesthetics on the phase behaviour of the dipalmitoylphosphatidylcholine model membrane. Electron spin resonance tetrametylpiperidinyloxyl partition study.

Using the electron spin resonance technique of the spin probe (TEMPO) is shown that local anaesthetics lidocaine, tetracaine, dibucaine, heptacaine and carbizocaine decrease the gel--liquid crystal phase transition temperature and increase the width of the phase transition of the dipalmitoylphosphatidylcholine (DPPC) model membrane. These effects roughly correlate with the efficiencies of the anesthetics to block action potential propagation in the nerves.

Anesthetics, Local↗
PubMed1983

A spin label study of the perturbation effect of tertiary amine anesthetics on brain lipid liposomes and synaptosomes.

The membrane disordering efficiency of four local anesthetics, including lidocaine, tetracaine, dibucaine and heptacaine (piperidinoethyl ester of 2-heptyloxyphenylcarbamic acid) has been studied by spin-labeling methods. The disordering efficiency of the drugs in rat total brain lipid liposomes was quantitated with the initial slope value of the order parameter versus drug concentration curve, the so-called change-in-order parameter value. Using the positional isomers of m-doxyl stearic acids (m = 5, 12 and 16), it has been demonstrated that the tested drugs reveal quite different disordering efficiency. There is a clear tendency of increasing disordering efficiency towards the methyl terminal of the lipid acyl chains. By a comparison of order parameter versus drug concentration and temperature at three depths of rat brain total lipid liposomes and synaptosomes, it is shown that the 'fluidizing effect' of local anesthetics does not correspond to fluidization of membrane by temperature and that tetracaine and dibucaine do not have equal disordering efficiency as judged by their solubility in the membrane. The disordering efficiency of these drugs on the hydrocarbone core of a membrane qualitatively corresponds to their anesthetic potency. Similar results were obtained in liposomes and synaptosomes. It is assumed that there is a similar incorporation of the local anesthetics in the liposomes and in the lipid part of synaptosomes.

Anesthetics, Local↗
PubMed1982

Facilitatory effect of some drugs on transmission in the frog sympathetic ganglion.

Effects of 3,4-diaminopyridine and dimethylsulfoxide on transmission in frog sympathetic ganglion were analyzed. In the presence of either drug repetitive waves appeared in the compound action potential. Intracellular recording revealed a repetitive firing of certain populations of ganglionic neurons following each orthodromic stimulus. Antidromic stimulation did not evoke any repetitive response. Dependence of the repetitive response on drug concentration and stimulation rate is described. An enhancement and prolongation of fast EPSP was observed in the presence of both drugs. It is assumed that by interference with changes in membrane potassium permeability the drugs prolong the action potential in presynaptic terminals with a resulting increase in synaptic output of transmitter. The repetitive firing of the postsynaptic membrane subsequent to activation of the synapse is a consequence of its prolonged and more profound depolarization. Presumably, this is one of several mechanisms of drug-induced increase in efficacy of synaptic transmission in frog sympathetic ganglion known as stimulus-bound repetition.

4-Aminopyridine↗
PubMedDate not supplied

Protective effect of stobadine, a pyridoindole antioxidant, in hypoxia-reoxygenation injury of ganglionic and hippocampal neurotransmission.

Hypoxia (HYP) followed by reoxygenation (REOX) occurs frequently in the pathophysiology of the CNS. Free oxygen radicals (FOR) may participate in cerebral injury under such circumstances. Pharmacological control of the generation and/or subsequent effects of FOR by new effective compounds might contribute to the treatment of disorders such as stroke and cerebral trauma. Effects of stobadine, a pyridoindole antioxidant that is able to interact with some FOR, were analyzed on synaptic transmission in rat superior cervical ganglia and hippocampal slices during HYP-REOX procedure in vitro. The amplitude of compound action potential in the ganglion evoked by supramaximal electrical stimulation of preganglionic nerve was reduced to approximately 20% of the control value during HYP (90 min). The action potential did not recover during REOX (60 min). Stobadine (10 mM) applied before, during, and after HYP, did not change the HYP-induced inhibition; however, a significant recovery of transmission (to 78.5% +/- 8.3) occurred during REOX. A similar effect was observed in the presence of the antioxidant Trolox (0.2 mM), a derivative of alpha-tocopherol. Stobadine, in concentrations of > 30 microM inhibited ganglionic transmission in a concentration-dependent manner. HYP lasting more than 2-3 min fully depressed field action potentials evoked in hippocampal CA1 region neurons by supramaximal electrical stimulation of Schäffer collaterals. If HYP exceeded 8 min, transmission did not recover during REOX. Stobadine (10 microM) applied during HYP significantly enhanced the probability of transmission recovery in the REOX period. Some preparations recovered following HYP lasting as long as 13-15 min. On applying the compound before, during, and after HYP that lasted for 8 min, the transmission recovery was 72.6% +/- 21.8 of the control value, compared to only 16.1% +/- 12.7 in the untreated preparations. In concentrations ranging from 0.3-1.73 mM, stobadine inhibited hippocampal transmission. Stobadine proved to be an effective agent in the protection of synaptic transmission against HYP-REOX-induced injury in both neuronal preparations studied in vitro. This effect might be linked to the antioxidant and free radical scavenging effects of stobadine.

Action Potentials↗
PubMedDate not supplied

Effect of antioxidants and NMDA antagonists on the density of NMDA binding sites in rat hippocampal slices exposed to hypoxia/reoxygenation.

Major interest is currently focused on the development and evaluation of effective strategies for the pharmacological therapy of human stroke and cerebral ischemia, as well as some neurodegenerative disorders in which increased production of free oxygen radicals and the neurotoxic effect of excitatory amino acids may take place. Selected N-methyl-D-aspartate (NMDA) antagonists and antioxidants in the model of experimental oxidative stress induced by hypoxia and reoxygenation in rat hippocampal slices were tested. The putative antiglutamatergic effect of the antioxidant stobadine and its neuroprotective effect during oxidative stress was studied. NMDA antaonists 2-amino-5-phosphonovaleric acid (APV) and Mg2+, as well as the antioxidants stobadine and trolox, prevented the decrease of NMDA binding site number induced by hypoxia/reoxygenation in rat hippocampal slices. Moreover, stobadine, APV and Mg2+ prevented the decrease of NMDA binding site number due to glutamic acid incubation. Stobadine does not inhibit [3H]-glutamate binding and therefore does not seem to interact directly with glutamate binding sites. Thus, its neuroprotective effect in rat hippocampus exposed to hypoxia/reoxygenation does not seem to be based on a direct antiglutamatergic effect. The protective action of stobadine against the decrease of NMDA binding site number elicited by hypoxia/reoxygenation in rat hippocampus could rather be due to its antioxidant and antiradical effect.

Animals↗