Incomplete sodium inactivation in nodes of ranvier treated with scorpion venom

Koppenhöfer, E; Schmidt, Hans

doi:10.1007/bf02136780

Cited by 56 publications

(14 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Potassium cannot be replaced by sodium, calcium, or magnesium ions which tend to inhibit labeled apamin binding when used in higher concentrations. The hypothesis should be checked that apamin interacts with membrane constituent(s) directed towards the extracellular space and involved in the handling of potassium, just as scorpion [12] or sea anemone toxins [13] are involved in keeping sodium channels open. Indeed apamin appears to alter the potassium permeability in primary nerve cell cultures [14].…”

Section: Quantitative Aspectsmentioning

confidence: 99%

Bee Venom Neurotoxin (Apamin): Iodine Labeling and Characterization of Binding Sites

Habermann

Fischer

1979

European Journal of Biochemistry

View full text Add to dashboard Cite

1. Apamin, the octadecapeptide from bee venom acting on the central nervous system, has been labeled with lz5I at its single histidine residue. Apamin, monoiodoapamin, diiodoapamin, and iodide can be separated on thin-layer chromatography. Diiodoapamin retains about half the toxicity of the original peptide. Partial iodination with leading mainly to the monoiodo derivative, did not measurably decrease the toxicity.2. Labeled apamin binds to the insoluble, but not to the soluble part of homogenates made from rat cerebral cortex. The order of binding to homogenates is rat forebrain > rostra1 part of the brain stem > cerebellum > caudal part of the brain stem > spinal cord. Grey substance of rabbit forebrain binds much better than white matter. The binding site is enriched within fractions of rat cerebral cortex which sediment between 10000 and 100000 xg. 3. Apamin also binds to peripheral organs. In rats, the sequence of specific apamin binding by different organs is cerebral cortex % (20x) liver > kidney or ileum whereas binding by skeletal muscle, salivary glands, and testes is hardly measurable. In rabbits, the sequence is cerebral cortex NN liver > adrenals > cerebellum > kidney > medulla oblongata, whereas skeletal muscle and ileal mucosa do not bind to a measurable degree. Among all organs tested, bovine adrenal cortex binds the most. 4. Binding data with rat cerebral cortex were obtained under a variety of conditions. A single type of binding sites occurred with a density of about 1-3 pmol/g rat forebrain (wet weight). A very high affinity (Kd in the range of 10-25 pM) was found in both equilibrium and velocity measurements.5. With increasing temperature apamin binding is diminished. Labeled apamin is slowly degraded by the supernatant of rat brain homogenate at 37 "C and 25 "C, but not at 5 "C.High specificity, high affinity and prevalence of binding sites within the nervous system indicate, together with the rank order of potency of apamin derivatives, a role of binding in poisoning. However, final proof will need a direct comparison between binding and the action of apamin on isolated systems.Apamin is a specific, centrally acting neurotoxic peptide from bee venom [l]. Its structure has been determined independently by two groups [2,3] and solid-phase syntheses of fully active apamin have been achieved in two laboratories [4,5].Apamin hardly enters the brain or spinal cord upon intravenous injection [6]. Accordingly, apamin administered by intraventricular injection or microinjection into the spinal cord is 1000-10000 times more toxic than by intravenous or subcutaneous injection. In mice and rats about 10 ng of apamin, given intraventricularly, elicit the typical signs of taining 0.85 % sodium chloride.Abbreviation. Tris-saline, 0.05 M Tris-HCI buffer pH 7.5, contoxicity: after a short period of slightly depressed activity, the animals suffer from uncoordinated and generalized motor hyperactivity which eventually leads to death. Animals which survive sublethal doses show signs of hyperactivity and/or hy...

show abstract

Section: Quantitative Aspectsmentioning

confidence: 99%

Bee Venom Neurotoxin (Apamin): Iodine Labeling and Characterization of Binding Sites

Habermann

Fischer

1979

European Journal of Biochemistry

View full text Add to dashboard Cite

show abstract

“…639 M. P. BLA USTEIN endings (Miledi, 1971), in squid axons (Baker, Meves & Ridgeway, 1973a) and in muscle fibres (Hagiwara & Nakajima, 1966); Mg enters squid axons during electrical activity, perhaps via the 'late Ca conductance' pathway (Baker & Crawford, 1972 (including synaptosomes) by increasing Na permeability (PNa), and the blockage of this effect by tetrodotoxin, was discussed in the preceding article (Blaustein & Goldring, 1975). Like veratridine, the venom of certain scorpions depolarizes cells with an Na-action potential (Adam & Weiss, 1959;Narahashi, Shapiro, Deguchi, Scuka & Wang, 1972) by blocking inactivation of the Na conductance mechanism (Koppenh6fer & Schmidt, 1968), thereby increasing PNa. The depolarizing action of scorpion venom is also prevented or reversed by tetrodotoxin (T. Narahashi, personal communication).…”

Section: Psmentioning

confidence: 99%

Effects of potassium, veratridine, and scorpion venom on calcium accumulation and transmitter release by nerve terminals in vitro.

Blaustein¹

1975

The Journal of Physiology

551

293

View full text Add to dashboard Cite

show abstract

“…Despite structural similarities among the various scorpion toxins, these proteins display wide variations in activity (5,6), and it is not clear if all of the scorpion toxins follow the same general mechanism of action (7). Several of the toxins have been shown to prolong the action potentials of excitable membranes by blocking the inactivation of sodium channels (8)(9)(10), an effect similar to that produced by sea anemone toxins (11). However, the scorpion toxin and sea anemone toxin binding sites appear to be distinct from those occupied by other…”

mentioning

confidence: 99%

Three-dimensional structure of a protein from scorpion venom: a new structural class of neurotoxins.

Fontecilla‐Camps¹,

Almassy²,

Suddath³

et al. 1980

Proc. Natl. Acad. Sci. U.S.A.

103

View full text Add to dashboard Cite

The three-dimensional crystal structure of variant-3 toxin from the scorpion Centruroides sculpturatus Ewing has been determined at 3 A resolution. Phases were obtained by use of K2PtCL4 and K2IrCl derivatives. The most prominent secondary structural features are two and a half turns of a-helix and a three-strand stretch of antiparallel a-sheet, which runs parallel to the a-helix. The helix is connected to the middle strand of the a-sheet by two disulfide bridges; a third disulfide bridge is located nearby. Several loops extend out of this dense core of secondary structure. The largest loop is joined to the COOH terminus of the molecule by the fourth disulfide bridge. The overall shape of the molecule resembles a right-hand fist: the a-helix runs along the knuckles of the fist; the a-sheet lies along the second and third joints of the fingers; the thumb is defined by two short loops that are composed of residues 16-21 and residues 41-46; the wrist corresponds to the COOHterminal stretch of residues 52-65 and a loop composed of residues 5-14; and the second joint of the little finger is near the NH2 terminus of the molecule. The a-carbon backbone displays a large flat surface that lies along the second joints of the fingers and the heel of the hand in the fist model. Several of the conserved residues in the scorpion neurotoxins are clustered on this surface, which may play a role in interactions of scorpion toxins with sodium channels of excitable membranes. Scorpion venoms contain sets of small basic proteins that are responsible for the neurotoxic activities of the venoms. These toxins display considerable variations in amino acid composition, but they generally consist of 60-70 amino acids and are crosslinked by four disulfide bridges. The partial or complete primary structures of about 25 toxins, from several different species of scorpions, have been determined (1). The amino acid sequences display a number of common features, including the same general locations of the eight cysteine residues, similar disulfide bridging patterns, and the location of several invariant or conserved residues. Thus, the available chemical data suggest that all of the scorpion toxins probably have similar threedimensional structures.The general effects of whole venoms or purified toxins injected in mammals are those expected from the massive release of neurotransmitters induced by depolarization of the nerve endings (2-4). Despite structural similarities among the various scorpion toxins, these proteins display wide variations in activity (5, 6), and it is not clear if all of the scorpion toxins follow the same general mechanism of action (7). Several of the toxins have been shown to prolong the action potentials of excitable membranes by blocking the inactivation of sodium channels (8-10), an effect similar to that produced by sea anemone toxins (11). However, the scorpion toxin and sea anemone toxin binding sites appear to be distinct from those occupied by otherThe publication costs of this article were defrayed in par...

show abstract

Incomplete sodium inactivation in nodes of ranvier treated with scorpion venom

Cited by 56 publications

References 13 publications

Bee Venom Neurotoxin (Apamin): Iodine Labeling and Characterization of Binding Sites

Bee Venom Neurotoxin (Apamin): Iodine Labeling and Characterization of Binding Sites

Effects of potassium, veratridine, and scorpion venom on calcium accumulation and transmitter release by nerve terminals in vitro.

Three-dimensional structure of a protein from scorpion venom: a new structural class of neurotoxins.

Contact Info

Product

Resources

About