Die Wirkung von Skorpiongift auf die Ionenstr�me des Ranvierschen Schn�rrings

Koppenhöfer, E; Schmidt, Hans

doi:10.1007/bf00592632

Cited by 89 publications

(18 citation statements)

References 9 publications

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“…If the tone did not spontaneously return to basal level, arginine vasopressin (AVP; 1 nM) was used to regain tone in preparations treated with scorpion venom. Scorpion venom is believed to inactivate nerves by opening of Na channels (Koppenhöfer and Schmidt 1968).…”

Section: Methodsmentioning

confidence: 99%

“…The venom acts by delaying the inactivation of Na channels (Koppenhöfer and Schmidt 1968), and might thereby cause transmitter release, followed by swollen nerve terminals depleted of synaptic vesicles (Daniel and Posey-Daniel 1984). Pig urethral smooth muscle exhibited a relaxation in response to scorpion venom, which might be due to release of a relaxant transmitter.…”

Section: Electron Microscopymentioning

confidence: 99%

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Neurotransmitter release evoked by α-latrotoxin in the smooth muscle of the female pig urethra

Werkström

Persson

et al. 1997

Naunyn-Schmiedeberg's Arch Pharmacol

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Neuronal regulation of smooth muscle tone in the female pig urethra has mainly been studied in vitro using electrical field stimulation (EFS) of nerves. Excitatory control is considered to be exerted by released noradrenaline, whereas inhibitory control is non-adrenergic non-cholinergic (NANC), and mediated by nitric oxide (NO), and an as yet unidentified agent. We investigated the functional and morphological effects of alpha-latrotoxin (alphaLTX), a spider neurotoxin believed to cause massive release of vesicle-stored neurotransmitters, on spontaneously developed urethral smooth muscle tone. The effects were compared to those of EFS and high potassium. In the presence of the NO-synthesis inhibitor N(omega)-nitro-L-arginine (L-NOARG: 0.3 mM) both alphaLTX and EFS evoked contractions. After treatment with scopolamine and phentolamine, no contraction was observed, and under these conditions alphaLTX and EFS induced relaxation. At low frequencies (<12 Hz), the EFS-induced relaxations were rapid, whereas at higher frequencies (>12 Hz), they were biphasic, consisting of a rapid first phase followed by a more long-lasting second phase. L-NOARG abolished the relaxations at low frequencies, as well as the first phase of the biphasic relaxation. The second phase was not affected by treatment with L-NOARG, but 0.1 microM omega-conotoxin GVIA, blocker of N-type voltage-operated calcium- channels (VOCCs), markedly reduced or abolished the response. In the presence of L-NOARG or omega-conotoxin GVIA, the alphaLTX-induced relaxation was significantly decreased, and the combination of L-NOARG and omega-conotoxin GVIA further reduced or abolished the relaxation. In preparations-treated with tetrodotoxin or scorpion venom, believed to inactivate nerves by acting on sodium channels, alphaLTX and EFS had no effects. alphaLTX-induced relaxation was not associated with changes in cyclic GMP or cyclic AMP content. High (80 mM) potassium solution induced a triphasic response of the preparation. A transient relaxation was followed by a restoration of tone, and then by a persistent relaxation. The persistent relaxation was slightly reduced by scorpion venom or L-NOARG, but reduced by 50% by a combination of L-NOARG and omega-conotoxin GVIA. Ultrastructural analysis of the urethral circular smooth muscle layer revealed a moderate amount of nerve profiles supplying the smooth muscle. In control preparations, the nerve profiles contained both small synaptic vesicles and large dense core vesicles. alphaLTX caused a major loss of both types of vesicle. The present data suggest that alphaLTX has the ability to release not only adrenergic and cholinergic transmitters, but also NANC mediators of relaxation, including NO, from nerve terminals in the urethra.

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Section: Methodsmentioning

confidence: 99%

Section: Electron Microscopymentioning

confidence: 99%

Neurotransmitter release evoked by α-latrotoxin in the smooth muscle of the female pig urethra

Werkström

Persson

et al. 1997

Naunyn-Schmiedeberg's Arch Pharmacol

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“…Well-studied examples include members of the long-chain scorpion toxin family which, in general, interact with the extracellular loops between S3 and S4 to stabilize the Na v channel voltage sensors in the activated or resting state 17; 18; 19; 88; 89 . Based on their functional effects, two classes of Na v channel scorpion toxins have been defined 90 .…”

Section: Voltage-gated Sodium Channel Toxinsmentioning

confidence: 99%

“…In general, toxins that interfere with voltage-gated ion channel function do so through two mechanisms: pore-blocking toxins inhibit ion flow by binding to the outer vestibule or within the ion conduction pore 15; 16 whereas gating-modifier toxins interact with a channel region that alters conformation during opening or inactivation to influence the gating mechanism 17; 18; 19 . As such, gating-modifier toxins constitute powerful tools for researchers seeking to address the unique challenges associated with voltage-gated ion channel voltage sensors as they undergo complex conformational changes during channel activation and inactivation.…”

Section: Introductionmentioning

confidence: 99%

From Foe to Friend: Using Animal Toxins to Investigate Ion Channel Function

Kalia

Milescu

Salvatierra

et al. 2015

Journal of Molecular Biology

151

124

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Ion channels are vital contributors to cellular communication in a wide range of organisms, a distinct feature that renders this ubiquitous family of membrane-spanning proteins a prime target for toxins found in animal venom. For many years, the unique properties of these naturally-occurring molecules have enabled researchers to probe the structural and functional features of ion channels and to define their physiological roles in normal and diseased tissues. To illustrate their considerable impact on the ion channel field, this review will highlight fundamental insights into toxin-channel interactions as well as recently developed toxin screening methods and practical applications of engineered toxins.

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“…Venoms from two species are of particular interest. Centruroides sculpturatus neurotoxins selectively alter the voltage dependence of sodium activation, or "m" gating (8), and neurotoxins isolated from Leiurus quinquestriatus characteristically slow the kinetics of sodium inactivation (9,10).…”

mentioning

confidence: 99%

Detergent extraction of a presumptive gating component from the voltage-dependent sodium channel.

Culp¹,

McKenzie²

1981

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

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A physiologically characterized radiolabeled neurotoxin complex obtained from venom of the scorpion Leiurus quinquestriatue has been used to identify -detergent-solubilized presumptive sodium channel components in sucrose gradients. This toxin-binding component is found in extracts prepared from three sources of excitable membrane but appears to Electrophysiological experiments have provided a quantitative description ofthe time and field dependence ofgating processes that regulate voltage-dependent sodium channels. In contrast there is, as yet, little information on the structure and organization of these channels. One approach to providing such information is that of using physiologically characterized animal neurotoxins as selective affinity ligands for the identification of sodium channel components. Two neurotoxins that have proven to be of particular value in this regard are tetrodotoxin (TIX) and saxitoxin (STX). Although structurally different, these molecules have very similar physiological activities, binding to voltage-dependent sodium channels with high affinity to produce a selective sodium conductance block (1). This interaction effectively inhibits ion transport through the channel but does not appear to alter either the kinetics or voltage dependence of the asymmetry currents associated with channel gating (2, 3). These toxins also appear to show considerable biochemical specificity, recognizing the sodium channel to the relative exclusion of other membrane proteins (4). STX and TTX have been used as affinity ligands for the identification and partial purification of a sodium channel component solubilized from eel electroplaque (5) and rat skeletal muscle (6). The solubilized toxin-binding component has a molecular weight of 200,000-300,000 and a -sedimentation coefficient near 9 S. A rapid loss of high-affinity toxin-binding activity occurs in the presence ofexcess detergent or during procedures that strip bound lipid from the solubilized channel component; thus purification of this component in an active form appears possible only if exogenous lipid is added to the solubilization and chromatography buffers (7).A second group ofneurotoxins that may be ofsignificant value in biochemical studies on the sodium channel are those obtained from scorpion venoms. Scorpion toxins selectively alter channel gating without substantially changing channel conductance. Venoms from two species are of particular interest. Centruroides sculpturatus neurotoxins selectively alter the voltage dependence of sodium activation, or "m" gating (8), and neurotoxins isolated from Leiurus quinquestriatus characteristically slow the kinetics of sodium inactivation (9, 10).Of the scorpion neurotoxins, those from Leiurus have been the most extensively employed in biochemical studies on the sodium channel. Work on this venom by Miranda et aL (11) led to the isolation of five neurotoxic components. These toxins appear to be structurally related in that they have molecular weights near 6600, lack methionine, and show ...

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Die Wirkung von Skorpiongift auf die Ionenstr�me des Ranvierschen Schn�rrings

Cited by 89 publications

References 9 publications

Neurotransmitter release evoked by α-latrotoxin in the smooth muscle of the female pig urethra

Neurotransmitter release evoked by α-latrotoxin in the smooth muscle of the female pig urethra

From Foe to Friend: Using Animal Toxins to Investigate Ion Channel Function

Detergent extraction of a presumptive gating component from the voltage-dependent sodium channel.

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