Participation of Na+ channels in the potentiation by Tityus serrulatus α-toxin TsTx-V of glucose-induced electrical activity and insulin secretion in rodent islet β-cells
| Autor: | José Roberto Giglio, Antonio Ari Gonçalves, Antonio C. Boschero, Everardo M. Carneiro, Sergio Marangoni, Marcos H. Toyama, Eliana de Cássia Arantes |
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| Rok vydání: | 2003 |
| Předmět: |
Agonist
medicine.medical_specialty Tityus serrulatus medicine.drug_class medicine.medical_treatment Neurotoxins Molecular Conformation Scorpion Venoms Tetrodotoxin Toxicology Sodium Channels Scorpions Islets of Langerhans Mice chemistry.chemical_compound Internal medicine Insulin Secretion medicine Animals Insulin Secretion Phylogeny B-Lymphocytes Veratridine geography geography.geographical_feature_category biology Electric Conductivity Antagonist Sodium Channel Agonists Islet biology.organism_classification Rats Glucose Endocrinology chemistry |
| Zdroj: | Toxicon. 41:1039-1045 |
| ISSN: | 0041-0101 |
| DOI: | 10.1016/s0041-0101(03)00086-2 |
| Popis: | The effects of TsTx-V, an alpha-toxin isolated from Tityus serrulatus venom, on electrical activity and insulin secretion by rodent pancreatic islet cells were studied. TsTx-V (5.6 microg/ml) depolarized mouse pancreatic beta-cells, diminished the membrane input resistance and increased the duration of the active phase of glucose-induced electrical activity. Similar results were observed with the Na(+) channel agonist veratridine (110 microM). Both agents potentiated glucose (8.3 mM)-induced insulin secretion in rat islet. In the presence of TsTx-V or veratridine, insulin secretion increased 2- and 1.4-fold over basal values, respectively (P0.001). The Na(+) channel antagonist tetrodotoxin (6 microM) significantly decreased glucose- and TsTx-V-induced insulin secretion (P0.001). TsTx-V also stimulated insulin secretion at low glucose concentrations (2.8 mM) whereas the beta-toxin, Ts-gamma (gamma toxin), also obtained from Tityus serrulatus venom, significantly reduced TsTx-V-induced secretion at sub- and suprathreshold concentrations of glucose. These results are consistent with a model whereby Na(+) channels participate in glucose-induced electrical activity. Alteration in the activity of these channels changes the length of time during which the beta-cell depolarizes, thereby altering the secretory behavior of the cell. The construction of a three-dimensional model for TsTx-V revealed a conserved core containing an alpha-helix and three beta-strands, with minor differences when compared with toxins from other scorpion venoms. |
| Databáze: | OpenAIRE |
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