The Experts below are selected from a list of 168 Experts worldwide ranked by ideXlab platform
Tobias Huth - One of the best experts on this subject based on the ideXlab platform.
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sea anemone toxin atx ii elicits a fiber dependent pain and enhances resurgent and persistent sodium currents in large sensory neurons
Molecular Pain, 2012Co-Authors: Alexandra B Klinger, Christian Alzheimer, Andrea S Link, Lisa K Kutsche, Ruth Sittl, Theresa E Schuy, Tal Hoffmann, Mirjam Eberhardt, Barbara Namer, Tobias HuthAbstract:Background Gain-of-function mutations of the nociceptive voltage-gated sodium channel Nav1.7 lead to inherited pain syndromes, such as paroxysmal extreme pain disorder (PEPD). One characteristic of these mutations is slowed fast-inactivation kinetics, which may give rise to resurgent sodium currents. It is long known that toxins from Anemonia sulcata, such as ATX-II, slow fast inactivation and skin contact for example during diving leads to various symptoms such as pain and itch. Here, we investigated if ATX-II induces resurgent currents in sensory neurons of the dorsal root ganglion (DRGs) and how this may translate into human sensations.
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sea anemone toxin atx ii elicits a fiber dependent pain and enhances resurgent and persistent sodium currents in large sensory neurons
Molecular Pain, 2012Co-Authors: Alexandra B Klinger, Christian Alzheimer, Andrea S Link, Lisa K Kutsche, Ruth Sittl, Theresa E Schuy, Tal Hoffmann, Mirjam Eberhardt, Barbara Namer, Tobias HuthAbstract:Background Gain-of-function mutations of the nociceptive voltage-gated sodium channel Nav1.7 lead to inherited pain syndromes, such as paroxysmal extreme pain disorder (PEPD). One characteristic of these mutations is slowed fast-inactivation kinetics, which may give rise to resurgent sodium currents. It is long known that toxins from Anemonia sulcata, such as ATX-II, slow fast inactivation and skin contact for example during diving leads to various symptoms such as pain and itch. Here, we investigated if ATX-II induces resurgent currents in sensory neurons of the dorsal root ganglion (DRGs) and how this may translate into human sensations.
Lászlo Béress - One of the best experts on this subject based on the ideXlab platform.
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natural abundance 13c nuclear magnetic resonance study of toxin ii from Anemonia sulcata
FEBS Journal, 2005Co-Authors: Raymond S Norton, Joachim Zwick, Lászlo BéressAbstract:Natural-abundance 13C NMR spectra (at 15.04 MHz) of the polypeptide toxin II from the sea anemone Anemonia sulcata have been analysed and compared with corresponding spectra reported recently for a closely related polypeptide anthopleurin A. The spectra contain many resolved onecarbon and two-carbon resonances from carbonyl, aromatic and methyl carbons, many of which have been assigned to individual carbons in the molecule on the basis of their chemical shifts, including their pH dependence, and by comparison with the 13C NMR spectrum of anthopleurin A. Analysis of the effects of pH on the spectrum yields estimates for the pKa values of a number of functional groups in the molecule, as follows: side-chain carboxylates of the two aspartic acid residues 2 and 3.1; COOH-terminal carboxylic acid, 3.5; imidazolium moieties of the two histidine residues, 6.7 and 7.6; NH2-terminal ammonium, 8. The similarity between the pKa values of these functional groups in toxin II and those of corresponding groups in anthopleurin A, together with the close agreement between chemical shifts of conserved curbons, indicates that many local interactions are nearly identical in the two molecules, and thus supports the thesis that their overall conformations in solution are similar. However, the local interactions involving one of the aspartic acid residues are altered in toxin II. Together with other data, this leads to a proposal for the site in these two molecules which is responsible for their cardiac stimulatory activity.
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biologically active polypeptides of Anemonia sulcata and of other sea anemones tools in the study of exitable membranes
Journal of Toxicology-toxin Reviews, 2005Co-Authors: Lászlo BéressAbstract:During the past thirty years sea anemones turned out to be important producer of biologically highly active polypeptides acting on Na+ and K+ ion channels. They are compoused from 27 to 59 aminoacids having molecular weights from 3000 to 7000 Da. All contain six cystein molecules which are interconnected to three sisulfide bridges. Because of their specifique mode of action on nerve cell exitation and on the mammalian heart muscle they became very important tools in neurophysiology and pharmacology. In the present review the research on sea anemone polypeptid toxins is summarized from a historical point of view, focussed on the polypeptides of Anemonia sulcata, Condylactis gigantea and Anthopleura elegantissima.
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A simple biochemical method in the search for bioactive polypeptides in a sea anemone (Anemonia sulcata).
Toxicon, 1996Co-Authors: J. Sanchez, Thomas Bruhn, Abel Aneiros, E. Wachter, Lászlo BéressAbstract:The sea anemone Anemonia sulcata is a well-known natural source of supply of biologically active polypeptides. So far, five toxins, ATX I, II, III, IV and AS V, several polyvalent protease inhibitors, an elastase inhibitor, two blood pressure-depressive polypeptides and very recently peptides that inhibit competitively the binding of 125I-dendrotoxin to rat brain membranes and block the voltage-sensitive K+ channels, have been isolated from it. The sea anemone toxins (especially toxin II of A. sulcata, ATX II) are very important tools in neurophysiological and pharmacological research, and their structure-function relationship has been investigated. Because of the great scientific value of the sea anemone toxins a simplification of their purification procedure was elaborated.
Raymond S Norton - One of the best experts on this subject based on the ideXlab platform.
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natural abundance 13c nuclear magnetic resonance study of toxin ii from Anemonia sulcata
FEBS Journal, 2005Co-Authors: Raymond S Norton, Joachim Zwick, Lászlo BéressAbstract:Natural-abundance 13C NMR spectra (at 15.04 MHz) of the polypeptide toxin II from the sea anemone Anemonia sulcata have been analysed and compared with corresponding spectra reported recently for a closely related polypeptide anthopleurin A. The spectra contain many resolved onecarbon and two-carbon resonances from carbonyl, aromatic and methyl carbons, many of which have been assigned to individual carbons in the molecule on the basis of their chemical shifts, including their pH dependence, and by comparison with the 13C NMR spectrum of anthopleurin A. Analysis of the effects of pH on the spectrum yields estimates for the pKa values of a number of functional groups in the molecule, as follows: side-chain carboxylates of the two aspartic acid residues 2 and 3.1; COOH-terminal carboxylic acid, 3.5; imidazolium moieties of the two histidine residues, 6.7 and 7.6; NH2-terminal ammonium, 8. The similarity between the pKa values of these functional groups in toxin II and those of corresponding groups in anthopleurin A, together with the close agreement between chemical shifts of conserved curbons, indicates that many local interactions are nearly identical in the two molecules, and thus supports the thesis that their overall conformations in solution are similar. However, the local interactions involving one of the aspartic acid residues are altered in toxin II. Together with other data, this leads to a proposal for the site in these two molecules which is responsible for their cardiac stimulatory activity.
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three dimensional structure in solution of neurotoxin iii from the sea anemone Anemonia sulcata
Biochemistry, 1994Co-Authors: Nick Manoleras, Raymond S NortonAbstract:The three-dimensional structure in aqueous solution of the 27-residue polypeptide neurotoxin Anemonia sulcata toxin III (ATX III) has been determined from 1H NMR data. As ATX III self-associates in the millimolar concentration range, causing a marked concentration dependence for the chemical shifts of several residues [Norton, R. S., Cross, K., Braach-Maksvytis, V., & Wachter, E. (1993) Biochem. J. 293, 545-551], it was necessary to record NOESY spectra over a range of concentrations in order to eliminate any intermolecular interactions from the NOE restraint set. The pairings of the six half-cystine residues were also unknown and had to be determined (as 3-17, 4-11, and 6-22) from preliminary structure calculations performed using both upper bound distance restraints from NOESY data and a substantial number of lower bound restraints inferred from the absence of NOESY cross-peaks. Final structures were determined, using the program X-PLOR, from interproton distance restraints inferred from NOEs, backbone and side chain dihedral angle restraints from spin-spin coupling measurements, and a smaller number of lower bound restraints. Stereospecific assignments for 11 beta-methylene pairs were also included. The final set of 28 structures had an average pairwise RMS difference of 1.32 A over the backbone heavy atoms (N, C alpha, and C) and 2.18 A over all heavy atoms. For the well-defined region encompassing residues 3-22, the corresponding values were 0.62 and 1.28 A, respectively. ATX III adopts a compact structure containing four reverse turns (a distorted type I beta-turn at residues 6-9, a type I beta-turn at residues 8-11, and inverse gamma-turns at residues 12-14 and 15-17) and two other chain reversals, but no regular alpha-helix or beta-sheet. Several of the residues most affected by aggregation are located on the surface of the molecule, forming a hydrophobic patch which may constitute part of the sodium channel binding surface. Possible relationships between the structure of ATX III and those of other sea anemone toxins that interact with the same site on the voltage-gated sodium channel are considered.
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1h n m r study of the solution properties and secondary structure of neurotoxin iii from the sea anemone Anemonia sulcata
Biochemical Journal, 1993Co-Authors: Raymond S Norton, Keith J Cross, V Braachmaksvytis, E. WachterAbstract:The solution properties, secondary structure and global fold of the 27-residue polypeptide neurotoxin III (ATX III), from the sea anemone Anemonia sulcata, have been investigated using high-resolution 1H-n.m.r. spectroscopy. Studies of the concentration dependence of the n.m.r. spectrum indicate that the molecule self-associates in the millimolar concentration range useable for n.m.r. analysis, the association being less pronounced at acidic pH values. The dependence on pH of association implies that electrostatic interactions play a role in this process, while the significant concentration-dependent shifts of the aromatic resonances of Tyr-7 and Trp-13 indicate that hydrophobic interactions also contribute. Individual pKa values have been determined for most ionizable groups in the molecule. Sequence-specific resonance assignments were obtained for all protons using a range of two-dimensional homonuclear-correlated and nuclear-Overhauser-effect (nOe) spectra. The secondary structure of the polypeptide was identified from sequential (i, i+1) and medium-range (i, i+2/3/4) nOe connectivities, NH to C alpha H coupling constants, C alpha H chemical shifts, and the location of slowly exchanging backbone-amide protons. ATX III contains no regular alpha-helix or beta-sheet, consisting instead of a network of reverse turns. nOe connectivities between half-cystine residues are consistent with the disulphide pairings 3-17, 4-11 and 6-22. ATX III has a well-defined structure and appears to lack the disordered loop which, in the longer sea anemone toxins (46-49 residues), may be part of the receptor-binding surface.
Alexandra B Klinger - One of the best experts on this subject based on the ideXlab platform.
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sea anemone toxin atx ii elicits a fiber dependent pain and enhances resurgent and persistent sodium currents in large sensory neurons
Molecular Pain, 2012Co-Authors: Alexandra B Klinger, Christian Alzheimer, Andrea S Link, Lisa K Kutsche, Ruth Sittl, Theresa E Schuy, Tal Hoffmann, Mirjam Eberhardt, Barbara Namer, Tobias HuthAbstract:Background Gain-of-function mutations of the nociceptive voltage-gated sodium channel Nav1.7 lead to inherited pain syndromes, such as paroxysmal extreme pain disorder (PEPD). One characteristic of these mutations is slowed fast-inactivation kinetics, which may give rise to resurgent sodium currents. It is long known that toxins from Anemonia sulcata, such as ATX-II, slow fast inactivation and skin contact for example during diving leads to various symptoms such as pain and itch. Here, we investigated if ATX-II induces resurgent currents in sensory neurons of the dorsal root ganglion (DRGs) and how this may translate into human sensations.
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sea anemone toxin atx ii elicits a fiber dependent pain and enhances resurgent and persistent sodium currents in large sensory neurons
Molecular Pain, 2012Co-Authors: Alexandra B Klinger, Christian Alzheimer, Andrea S Link, Lisa K Kutsche, Ruth Sittl, Theresa E Schuy, Tal Hoffmann, Mirjam Eberhardt, Barbara Namer, Tobias HuthAbstract:Background Gain-of-function mutations of the nociceptive voltage-gated sodium channel Nav1.7 lead to inherited pain syndromes, such as paroxysmal extreme pain disorder (PEPD). One characteristic of these mutations is slowed fast-inactivation kinetics, which may give rise to resurgent sodium currents. It is long known that toxins from Anemonia sulcata, such as ATX-II, slow fast inactivation and skin contact for example during diving leads to various symptoms such as pain and itch. Here, we investigated if ATX-II induces resurgent currents in sensory neurons of the dorsal root ganglion (DRGs) and how this may translate into human sensations.
Linghao Kong - One of the best experts on this subject based on the ideXlab platform.
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sophocarpine attenuates the na dependent ca2 overload induced by Anemonia sulcata toxin increased late sodium current in rabbit ventricular myocytes
Journal of Cardiovascular Pharmacology, 2012Co-Authors: Shuo Zhang, Peihua Zhang, Antao Luo, Zhiqiang Ren, Linghao KongAbstract:Many studies indicate that an increase in late sodium current (I(Na.L)) of cardiomyocytes causes intracellular Na overload and subsequently raises the reverse Na/Ca exchanger current (INCX), ultimately resulting in intracellular Ca overload. Therefore, using drugs to inhibit the increased INa.L under various pathological conditions can lower intracellular Ca overload. This study was intended to explore the effect of sophocarpine (SOP) on the increase in INa.L, INCX, calcium transient and contraction in rabbit ventricular myocytes induced by Anemonia sulcata toxin II (ATX II), an opener of sodium channel, with the application of whole-cell patch-clamp techniques, the video-based motion edge detection system, and the intracellular calcium concentration determination system. The results indicate that tetrodotoxin (TTX, 4 μM ) obviously decreased INa.L and INCX enlarged by ATX II (30 nM), and SOP (20, 40, and 80 μM) also inhibited both the parameters concentration dependently in rabbit ventricular myocytes. However, transient sodium current remained unaffected by the above-mentioned concentrations of ATX II, TTX, and SOP. In addition, SOP also reversed diastolic calcium concentration, calcium transient amplitude, and ventricular muscle contractility augmented by ATX II. Its effects were similar to those of TTX, a specific inhibitor of the sodium channel. In conclusion, SOP inhibits INa.L, INCX, diastolic Ca concentration, and contractility in rabbit ventricular myocytes, which suggests that relief of intracellular Ca overload through inhibiting INa.L is likely to become a new therapeutic mechanism of SOP against arrhythmia and myocyte damage associated with intracellular Ca overload.