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Preferential action of β-bungarotoxin at nerve terminal regions in the hippocampus
Hebrew University of Jerusalem, Jerusalem, Israel, and Laboratory of Physiology, School of Medicine, Angers, France) Insect toxic components from the venom of a chactoid scorpion, Scorpio mourus palmatus (Scorpionidae) . J. biol. Chem . 257, 8397 (1982) . SEVERAL, insect toxic components were isolated from the venom of the chactoid scorpion, Scorpio mourus palmatus (Scorpionidae) by column chromatography, with the following findings . The toxicity of the crude venom to insects is due to three separate groups of substances, the so-called cytotoxins, phospholipases and neurotoxins, which play a dominant role . The neurotoxic fraction contains two factors: the fast reversibly paralytic and the slow lethal . The slow lethal factor is composed of two toxins (IT, and IT,), the purity of which was assessed by column chromatography, disc electrophoresis, isoelectrofocusing, analytical ultracentrifugation and amino acid analyses . IT, and IT, are two polypeptides possessing unique amino acid compositions with molecular weights of 3232 and 3963, pI's of 8.8 and 9.2, and supposed to contain two and three disulfide bridges, respectively . A clear cooperative interaction was demonstrated between the fast paralytic and lethal fractions, as well as betweenthe two insect toxins, resulting in an evident recovery of the original toxicity to insects of the crude venom . When assayed on an isolated insect axonal preparation under current and voltage clamp conditions, the combination of IT, and IT, caused a reversible block of both the sodium and potassium currents . This may explain the specific symptomatology and the mechanism of the paralysis induced by these toxins to an insect . The abovedata were compared with information concerning buthoid scorpion venom insect toxins . (Authors abstract)
H. P. Kotes
FRm, L. C. and MAUxo, A. (Rockefeller University, New York, NY 10021, U.S .A .) The ionic dependence of black widow spider venom action at the stretch receptor neuron and neuromuscular junction of crustaceans . J. Neurobiol. 13, 385 (1982) . THE EFFECTS of black widow spider venom (BWSV) on the crayfish stretch receptor and the lobster neuromuscular junction were examined . In crayfish stretch receptor neurons, BWSV caused a slight hyperpolarization followed by a large depolarization . The venom-induced depolarization of the stretch receptor was caused by an increase in membrane conductance to Na' and Ca'* . Black widow spider venom also caused an increase in the frequency of miniature inhibitory postsynaptic potentials recorded in the stretch receptor . The ability of BWSV to increase the frequency of miniature excitatory postsynaptic potentials (MEPSPs) at the lobsterneuromuscularjunction was dependent on the divalent cation composition of the bathing medium . Ringer solutions containing Ca" supported the greatest venom-induced increase in MEPSP frequency, Mg" and Mn" supported a moderate increase in MEPSP frequency, while Co'* and Zn'* blocked this venom effect entirely . Black widow spider venom did not block axonal conduction in lobster walking leg axons or in the axon of the crayfish stretch receptor . The results suggest that in crustaceans, BWSV interacts specifically with membrane of the soma - dendritic region of the stretch receptor and with nerve terminal membrane, causingan increase in Na" andCa'* conductance. (Authors abstract)
H. P . KOLM
WALL, P. D., Mn,t.s, R., FITZGERALD, M . and GtasoN, S. J. (Cerebral Functions Group, Department of Anatomy, University College London, London WCIE 6BT, U.K .) Chronic blockade of sciatic nerve transmission by tetrodotoxin does not produce central changes in the dorsal horn of the spinal cord of the rat. Neurosci. Lett . 30, 315 (1982) . RAT sciAr~c rvERVES were treated with tetrodotoxin (TTX) for 4- 10 days, by implanting a glass capillary tube filled with TTX into the nerve through the epineurium . Following this treatment the somatotopic organization of receptive fields in the L4 dorsal horn cells was mapped . This was done by making a series of microelectrode tracks through the medial L4 dorsal horn, an area of cord normally responding only to foot stimulation . The map was normal in animals treated with TTX. Dorsal horn levels of fluoride-resistant acid phosphatase, substance P, somatostatin, cholecystokinin-like peptide, neurotensin and neurophysin were also normal as assessed from density of staining . These results are discussed in the light of the positive changes that are seen following chronic sciatic nerve section . (Authors abstract)
H. P. KOLA?
HALLIWELL, J. V. and DOLLY, J . O. (Department of Pharmacology, School of Pharmacy, University of London, and Department of Biochemistry, Imperial College, London, U.K .) Preferential action of ß-bungarotoxin at nerve terminal regions in the hippocampus. Neurosci. Lett. 30, 321 (1982) .
THE AcrioN of ß-bungarotoxin on thetransverse slice of rat hippocampus has been studied in vitro . The toxin (230 nM) initially impaired neurotransmission in the major subdivisions of the slice with a half time for blockade of about 10 min. Intracellular recordings revealed no reduction in pyramidal cell sensitivity to putative neurotransmitters, suggesting a primary action of the toxin upon transmitter release . More protracted effects of ß-bungarotoxin included a reduction of neuronal excitability, particularly in the terminal regions of hippocampal fibre pathways, but these proceeded at a much slower rate than the action on synaptic transmission . It is
Reviews
489
concluded that the toxin binds to some component present at terminal regions to mediate its preferential effect in the hippocampus. (Authors abstract)
H. P. KOLM
JAIMOVICH, E., ILDEFONSE, M., BnItHnrItIV, J . GOUGIER, O. and LAZDUNSKI, M. (Centre de Biochimie du CNRS, Faculté des Sciences, Parc Valrose, 06034 Nice Cedex, and Laboratoire de Physiologie des Éléments Excitables, Université Claude Bernard, F~9621 Villeurbanne, France) Centruroides toxin, a selective Mocker of surface Na* channels in skeletal muscle: voltage-clamp analysis and biochemical characterization of the receptor . Proc . natn . Acad. Sci. U.S .A .79, 3896(1982) . THIS PAPER describes the effects of a toxin from the scorpion Centruroides sgffusus suffuses on frog skeletal muscle . The main findings are the following. (i) Centruroides toxin (Css II) blocks the early phase of the inward sodium current in the muscle that arises from influx via Na* channels in the surface membrane, but it does not affect the late phase of the inward current that represents flux through Na* channels in the T-tubule membranes. (ü) CssII , in marked contrast to tetrôdotoxin, does not affect contraction of the muscle . (üi) Measurements of the binding of "°I-labeled Csstl to a partially purified membrane preparation from the muscle indicate that theKd of the Css - receptor complex Is -=A.4 nM . The half-life for the dissociation of this complex is 3 min at 22°C and 16 min at ~°C. Binding of the radiolabeled toritt varies markedly with pH and becomes insignificant at pH >8 .5 . Proteolytic digestion of the membrane preparation decreases its ability to bind Csslt , suggesting that the receptor is a protein. (iv) The number of binding sites for a radiolabeled derivative of tetrodotoxin on the membrane preparation was similar to that for Csstl . However, neither tetrodotoxin nor any of seven other neurotoxins and some local anesthetics that alter the functioning of the Na* channel have any effect on the binding of Csslt to the muscle membrane . These results therefore indicate that Csstl belongs to a different class of neurotoxins that has a different receptor on the Na* channel . (Authors abstract)
H . P. KOLM
Ft,oEHSHEInt, G. L., WEHER, O., TSCHUMI, P. and ULBRICH, M. Die klinische Knollenblätterpilzvergiftung (Amarritaphalloides): prognostische Faktoren und therapeutische Maßnahmen. Schweiz. med. Wschr. 112, l 164 (1982) . TWO-IiUNDHED and five cases of clinical poisoning with the mushroom Amanita phalloides (death cap) in the period 1971-1980 have been studied retrospectively. The lethality was 22 .4%. Age and latency between the ingestion of the mushrooms and the first clinical symptoms were of prognostic significance . The death rate was S 1 .3 % in children below 10 years of agebutonly 16.Solo in patients olderthan 10 years. The average latencyperiod was 10 .3 hours for the fatal cases and 12 .6 hours for the surviving patients . Country, year, sex and time of hospitalization did not influence lethality. Prognostic relevance could also be attributed to the thromboplastin time . Eighty-four per cent of the patients with values below 10% died, while all patients with minimal values of more than 40% survived . The correlation with the outcome was weaker for the serum rranaan, inases and nil for creatinine . The patients underwent, on the average, 8 therapeutic measures, but up to 20 therapies could be administered to the same patient. Eight of the 30 recorded treatments involved general support, 7 toxin elimination and the remaining 14 could be classified as pharmacotherapy. With the aid of multiple regression analysis taking into account age, latency period and the effects of all the other measures, penicillin and hyperbaric oxygenation were found to contribute independently to a higher survival rate . As compared to penicillin, the combination of penicillin with silybin wasassociated with still further increased survival . On the other hand, several measures, including exchange transfusion, thioctic acid, sulfamethoxazole, plasma expanders, haemodialysis, treatment of the hemorrhagic diathesis and THAM/sodium bicarbonate were administered more often to patients who did not survive. For the remaining 20 therapeutic measures our analysis revealed neither a positive nor anegative correlation with theclinical outcome. (Authors abstract)
H. P. KOLM
BRAEKMAN, J . C., D,v-ozE, D., MACeno DE AHREU, P., PICCINM-LEOPARDI, C., GERtKnirt, G. and vwty MEERSSCFII:, M. (Collectif de Bio-Écologie, Faculté des Sciences, Université Libre de Bruxelles, 1050 Brussels, Belgium) A novel type of bin-quinolizidine alkaloid from thesponge Petrasia scruta. Tetrahedron Lett. 23, 4277 (1982). THE srttucrunE of petrosin, the major alkaloid isolated from the sponge Petrosia seriata, hasbeen determined by X-ray diffraction analysis . Petrosin is the first meatber of a new class of bis-quinolizidine alkaloids containing a C-16 macrocycle . (Authors abstract)
H. P. KOLM
1JEMlJRA, M., SHIMADf,, K., TOxUYAMA, T. and D,v.v J. W. (Faculty of Science, Osaka City University, Sugimoto-3, Sumiyoshi-ku, Osaka 558, Japan, and National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases, NIB, Hethesda, MD 20205, U.S .A .) The absolute configuration of the side chain diol moiety of the poison-frog alkaloid pumiüotoxin B. TetrahedronLett. 23, 4369 (1982) .
H. P. Kotes
FRm, L. C. and MAUxo, A. (Rockefeller University, New York, NY 10021, U.S .A .) The ionic dependence of black widow spider venom action at the stretch receptor neuron and neuromuscular junction of crustaceans . J. Neurobiol. 13, 385 (1982) . THE EFFECTS of black widow spider venom (BWSV) on the crayfish stretch receptor and the lobster neuromuscular junction were examined . In crayfish stretch receptor neurons, BWSV caused a slight hyperpolarization followed by a large depolarization . The venom-induced depolarization of the stretch receptor was caused by an increase in membrane conductance to Na' and Ca'* . Black widow spider venom also caused an increase in the frequency of miniature inhibitory postsynaptic potentials recorded in the stretch receptor . The ability of BWSV to increase the frequency of miniature excitatory postsynaptic potentials (MEPSPs) at the lobsterneuromuscularjunction was dependent on the divalent cation composition of the bathing medium . Ringer solutions containing Ca" supported the greatest venom-induced increase in MEPSP frequency, Mg" and Mn" supported a moderate increase in MEPSP frequency, while Co'* and Zn'* blocked this venom effect entirely . Black widow spider venom did not block axonal conduction in lobster walking leg axons or in the axon of the crayfish stretch receptor . The results suggest that in crustaceans, BWSV interacts specifically with membrane of the soma - dendritic region of the stretch receptor and with nerve terminal membrane, causingan increase in Na" andCa'* conductance. (Authors abstract)
H. P . KOLM
WALL, P. D., Mn,t.s, R., FITZGERALD, M . and GtasoN, S. J. (Cerebral Functions Group, Department of Anatomy, University College London, London WCIE 6BT, U.K .) Chronic blockade of sciatic nerve transmission by tetrodotoxin does not produce central changes in the dorsal horn of the spinal cord of the rat. Neurosci. Lett . 30, 315 (1982) . RAT sciAr~c rvERVES were treated with tetrodotoxin (TTX) for 4- 10 days, by implanting a glass capillary tube filled with TTX into the nerve through the epineurium . Following this treatment the somatotopic organization of receptive fields in the L4 dorsal horn cells was mapped . This was done by making a series of microelectrode tracks through the medial L4 dorsal horn, an area of cord normally responding only to foot stimulation . The map was normal in animals treated with TTX. Dorsal horn levels of fluoride-resistant acid phosphatase, substance P, somatostatin, cholecystokinin-like peptide, neurotensin and neurophysin were also normal as assessed from density of staining . These results are discussed in the light of the positive changes that are seen following chronic sciatic nerve section . (Authors abstract)
H. P. KOLA?
HALLIWELL, J. V. and DOLLY, J . O. (Department of Pharmacology, School of Pharmacy, University of London, and Department of Biochemistry, Imperial College, London, U.K .) Preferential action of ß-bungarotoxin at nerve terminal regions in the hippocampus. Neurosci. Lett. 30, 321 (1982) .
THE AcrioN of ß-bungarotoxin on thetransverse slice of rat hippocampus has been studied in vitro . The toxin (230 nM) initially impaired neurotransmission in the major subdivisions of the slice with a half time for blockade of about 10 min. Intracellular recordings revealed no reduction in pyramidal cell sensitivity to putative neurotransmitters, suggesting a primary action of the toxin upon transmitter release . More protracted effects of ß-bungarotoxin included a reduction of neuronal excitability, particularly in the terminal regions of hippocampal fibre pathways, but these proceeded at a much slower rate than the action on synaptic transmission . It is
Reviews
489
concluded that the toxin binds to some component present at terminal regions to mediate its preferential effect in the hippocampus. (Authors abstract)
H. P. KOLM
JAIMOVICH, E., ILDEFONSE, M., BnItHnrItIV, J . GOUGIER, O. and LAZDUNSKI, M. (Centre de Biochimie du CNRS, Faculté des Sciences, Parc Valrose, 06034 Nice Cedex, and Laboratoire de Physiologie des Éléments Excitables, Université Claude Bernard, F~9621 Villeurbanne, France) Centruroides toxin, a selective Mocker of surface Na* channels in skeletal muscle: voltage-clamp analysis and biochemical characterization of the receptor . Proc . natn . Acad. Sci. U.S .A .79, 3896(1982) . THIS PAPER describes the effects of a toxin from the scorpion Centruroides sgffusus suffuses on frog skeletal muscle . The main findings are the following. (i) Centruroides toxin (Css II) blocks the early phase of the inward sodium current in the muscle that arises from influx via Na* channels in the surface membrane, but it does not affect the late phase of the inward current that represents flux through Na* channels in the T-tubule membranes. (ü) CssII , in marked contrast to tetrôdotoxin, does not affect contraction of the muscle . (üi) Measurements of the binding of "°I-labeled Csstl to a partially purified membrane preparation from the muscle indicate that theKd of the Css - receptor complex Is -=A.4 nM . The half-life for the dissociation of this complex is 3 min at 22°C and 16 min at ~°C. Binding of the radiolabeled toritt varies markedly with pH and becomes insignificant at pH >8 .5 . Proteolytic digestion of the membrane preparation decreases its ability to bind Csslt , suggesting that the receptor is a protein. (iv) The number of binding sites for a radiolabeled derivative of tetrodotoxin on the membrane preparation was similar to that for Csstl . However, neither tetrodotoxin nor any of seven other neurotoxins and some local anesthetics that alter the functioning of the Na* channel have any effect on the binding of Csslt to the muscle membrane . These results therefore indicate that Csstl belongs to a different class of neurotoxins that has a different receptor on the Na* channel . (Authors abstract)
H . P. KOLM
Ft,oEHSHEInt, G. L., WEHER, O., TSCHUMI, P. and ULBRICH, M. Die klinische Knollenblätterpilzvergiftung (Amarritaphalloides): prognostische Faktoren und therapeutische Maßnahmen. Schweiz. med. Wschr. 112, l 164 (1982) . TWO-IiUNDHED and five cases of clinical poisoning with the mushroom Amanita phalloides (death cap) in the period 1971-1980 have been studied retrospectively. The lethality was 22 .4%. Age and latency between the ingestion of the mushrooms and the first clinical symptoms were of prognostic significance . The death rate was S 1 .3 % in children below 10 years of agebutonly 16.Solo in patients olderthan 10 years. The average latencyperiod was 10 .3 hours for the fatal cases and 12 .6 hours for the surviving patients . Country, year, sex and time of hospitalization did not influence lethality. Prognostic relevance could also be attributed to the thromboplastin time . Eighty-four per cent of the patients with values below 10% died, while all patients with minimal values of more than 40% survived . The correlation with the outcome was weaker for the serum rranaan, inases and nil for creatinine . The patients underwent, on the average, 8 therapeutic measures, but up to 20 therapies could be administered to the same patient. Eight of the 30 recorded treatments involved general support, 7 toxin elimination and the remaining 14 could be classified as pharmacotherapy. With the aid of multiple regression analysis taking into account age, latency period and the effects of all the other measures, penicillin and hyperbaric oxygenation were found to contribute independently to a higher survival rate . As compared to penicillin, the combination of penicillin with silybin wasassociated with still further increased survival . On the other hand, several measures, including exchange transfusion, thioctic acid, sulfamethoxazole, plasma expanders, haemodialysis, treatment of the hemorrhagic diathesis and THAM/sodium bicarbonate were administered more often to patients who did not survive. For the remaining 20 therapeutic measures our analysis revealed neither a positive nor anegative correlation with theclinical outcome. (Authors abstract)
H. P. KOLM
BRAEKMAN, J . C., D,v-ozE, D., MACeno DE AHREU, P., PICCINM-LEOPARDI, C., GERtKnirt, G. and vwty MEERSSCFII:, M. (Collectif de Bio-Écologie, Faculté des Sciences, Université Libre de Bruxelles, 1050 Brussels, Belgium) A novel type of bin-quinolizidine alkaloid from thesponge Petrasia scruta. Tetrahedron Lett. 23, 4277 (1982). THE srttucrunE of petrosin, the major alkaloid isolated from the sponge Petrosia seriata, hasbeen determined by X-ray diffraction analysis . Petrosin is the first meatber of a new class of bis-quinolizidine alkaloids containing a C-16 macrocycle . (Authors abstract)
H. P. KOLM
1JEMlJRA, M., SHIMADf,, K., TOxUYAMA, T. and D,v.v J. W. (Faculty of Science, Osaka City University, Sugimoto-3, Sumiyoshi-ku, Osaka 558, Japan, and National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases, NIB, Hethesda, MD 20205, U.S .A .) The absolute configuration of the side chain diol moiety of the poison-frog alkaloid pumiüotoxin B. TetrahedronLett. 23, 4369 (1982) .