Bencsik K

Bio: Bencsik K is an academic researcher from Albert Szent-Györgyi Medical University. The author has contributed to research in topics: Semipermeable membrane & Anticonvulsant. The author has an hindex of 3, co-authored 3 publications receiving 55 citations.

Naltrexone potentiates 4-aminopyridine seizures in the rat.

Abstract: The effects of a pharmacological blockade of the mu opiate receptors on the manifestation of tonic-clonic seizures were investigated in freely moving animals. 4-aminopyridine, a specific blocker of the neuronal K+ channels was used to produce generalized convulsions. After pretreatment of adult rats with 1 mg/kg naltrexone HCl, 3, 5, 7, 9, 14 mg/kg 4-aminopyridine was injected intraperitoneally, and the latencies of the symptoms generated by 4-aminopyridine were measured. Naltrexone HCl decreased these latencies and enhanced the seizures significantly. The experiments provided further evidence for the existence of a tonic anticonvulsant opioid system in the brain.

Pharmacological inhibition of brain carbonic anhydrase protects against 4-aminopyridine seizures.

Abstract: The effects of the inhibition of carbonic anhydrase on the manifestation of tonic-clonic seizures were investigated in freely-moving rats. 4-Aminopyridine, a specific blocker of the neuronal K+ channels was used to produce generalized convulsions. After pretreatment of adult male rats with 20 or 40 mg/kg acetazolamide, 3, 5, 7 or 9 mg/kg 4-aminopyridine was injected intraperitoneally and the latencies of the symptoms were measured. Pharmacological inhibition of brain carbonic anhydrase significantly increased the latency of onset of seizures. Bolus administration of acetazolamide decreased the incidence of generalized convulsions and protected against status epilepticus. Chronic acetazolamide treatment for 2 days affected only the generalized convulsions. The results suggested that alterations of the extracellular and intracellular pH by acetazolamide decreased the efficacy of synaptic transmission in several areas of the brain. The possible effects of the HCO3- ions on the sensitivity of synaptic and nonsynaptic neuronal receptors are discussed.

A modified semipermeable membrane technique for carbonic anhydrase histochemistry of the nervous system.

Abstract: We present a modification of Hansson's method for the demonstration of carbonic anhydrase activity. Using a semipermeable membrane together with a fluid incubation medium, frozen sections of aldehyde-fixed tissue were incubated without floating or dipping. Thin sections (thickness, 20–40 μm) were mounted on the outer surface of a tubularshaped, semipermeable cellophane dialysis membrane containing the incubation fluid. After incubation for 25–30 min at room temperature, the sections were rinsed in buffer and treated with 0.5% (NH4)2S solution. The histochemical reaction was fully inhibited by 10−4M acetazolamide.

4-aminopyridine-induced epileptiform activity and a GABA-mediated long- lasting depolarization in the rat hippocampus

Abstract: Two types of spontaneous filed potentials were recorded in rat hippocampal slices after addition of 4-aminopyridine (4-AP; 50 microM). One consisted of brief, epileptiform discharges that occurred at 0.6 +/- 0.2 sec-1 in the CA3 and CA1 areas. The other type occurred less frequently (0.036 +/- 0.013 sec-1) and was recorded in CA1, CA3, and dentate areas. It corresponded in all regions to an intracellular long-lasting depolarization (LLD; duration, 300-1200 msec; peak amplitude, 2-15 mV) that was abolished by bicuculline methiodide; therefore, it was mediated by GABAA receptors. Sectioning experiments and the occurrence of propagation failures indicated that LLDs could be initiated by any area of the slice. Furthermore, the propagation of LLDs did not follow any consistent or predictable pattern along known anatomical hippocampal pathways. Finally, neither the occurrence nor the propagation of LLDs was affected when excitatory synaptic transmission was blocked by NMDA and non-NMDA receptor antagonists. In the presence of antagonists of glutamatergic receptors, LLDs disappeared after the omission of Ca2+ or the addition of Cd2+ to the perfusing solution, suggesting that synaptic transmission was required for their generation. These data indicate that 4-AP discloses both interictal epileptiform discharges and LLDs in the rat hippocampus. The first type of activity is presumably related to certain properties of CA3 pyramidal neurons and the neuronal circuit, whereas LLDs originate from the spontaneous, periodic activity of GABAergic interneurons located in any area of the hippocampus, and can propagate to the other areas by the use of nonsynaptic mechanisms. We propose that 4-AP reveals a novel type of interaction among GABAergic interneurons that is based on the accumulation and the dispersion of K+.

Carbonic anhydrase inhibitor sulthiame reduces intracellular pH and epileptiform activity of hippocampal CA3 neurons.

Abstract: Summary: Purpose: Sulthiame is a carbonic anhydrase (CA) inhibitor with an anticonvulsant effect in the treatment of benign and symptomatic focal epilepsy in children. The aim of the study was to elucidate the mode of action of sulthiame with respect to possible changes of intracellular pH (pHi) that might develop along with sulthiame’s anticonvulsant properties. Methods: The effects of sulthiame (a) on pHi of 2,7-bis(2carboxyethyl)-5(6)-carboxyfluorescein-acetoxymetyl ester (BCECF-AM) loaded CA3 neurones as well as (b) on epileptiform activity (induced by 50 M 4-aminopyridine) were compared with those of the CA inhibitors acetazolamide and benzolamide. Results: In the majority of neurons, sulthiame (1.0–1.5 mM; n 8) as well as the membrane permeant acetazolamide (0.5– 1.0 mM; n 6) reversibly decreased pHi by 0.18 ± 0.05 (SD) and 0.17 ± 0.10 (SD) pH units, respectively, within 10 min. The poor membrane permeant benzolamide (1.0–2.0 mM) had no influence on pHi (n 8). Sulthiame (1.0–2.5 mM) and acetazolamide (1.0–2.0 mM) reversibly reduced the frequency of action potentials and epileptiform bursts after 10–15 min (n 9, n 7), whereas benzolamide (1.0–2.0 mM) had no effect (n 6). Conclusions: The results suggest that sulthiame acts as a membrane-permeant CA inhibitor whose beneficial effect on epileptiform activity results at least in part from a modest intracellular acidosis of central neurons. Key Words: Sulthiame—Intracellular pH—Benzolamide—Acetazolamide— Carbonic anhydrase inhibitor.

Membrane-bound carbonic anhydrase in human retinal pigment epithelium.

Abstract: Purpose. Inhibition of carbonic anhydrase (CA) by acetazolamide causes a decrease in the standing potential of the retinal pigment epithelium (RPE) and an increase in the rate of subretinal fluid absorption, and it may improve cystoid macular edema. These effects are thought to be mediated by the RPE. Given the solubility coefficient of acetazolamide, the drug is most likely to act by direct inhibition of membrane-bound CA (CA IV). To identify a substrate for acetazolamide in the RPE, the distribution of CA activity and the isoform of CA in the RPE membrane were investigated. Methods. Carbonic anhydrase activity was determined by Hansson's technique in fresh human eyes from donors of both sexes and different ages. The presence of the membrane-bound isoform CA IV was investigated immunohistochemically at the light and electron microscopic level, as well as by Western blotting in fresh RPE, and in adult and fetal RPE cultures. Results. Hansson's histochemical method demonstrated CA activity on the apical and basolateral cell membrane of the RPE. Using the y-globulin fraction of a polyclonal antibody against pure CA IV, immunocytochemistry showed labeling for CA IV on the apical RPE membrane of morphologically polarized human adult and fetal RPE cultures. Gel electrophoresis and Western blotting demonstrated a major immunoreactive band at 55 kDa in homogenates, which was consistently reduced to approximately 35 kDa by incorporation of 0.1% Triton X100 detergent. Conclusions. These results suggest that the clinical effects of carbonic anhydrase inhibitors on RPE function may be mediated via membrane-bound carbonic anhydrase activity in RPE and that CA FV is responsible for activity on the apical surface. Invest Ophthalmol Vis Sci. 1994; 35:3401-3407.