Participation of Na(+) channels in the potentiation by Tityus serrulatus alpha-toxin TsTx-V of glucose-induced electrical activity and insulin secretion in rodent islet beta-cells.
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 (P<0.001). The Na(+) channel antagonist tetrodotoxin (6 microM) significantly decreased glucose- and TsTx-V-induced insulin secretion (P<0.001). 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.
Gonçalves
Antonio A
AA
Departamento de Fisiologia e Biofísica, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), CP 6109, CEP 13083-970 Campinas SP, Brazil.
Toyama
Marcos H
MH
Carneiro
Everardo M
EM
Marangoni
Sergio
S
Arantes
Eliana C
EC
Giglio
José R
JR
Boschero
Antonio C
AC
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000502:physiology; D004553:Electric Conductivity; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008968:Molecular Conformation; D009498:Neurotoxins / Q000235:genetics / Q000494:pharmacology; D010802:Phylogeny; D051381:Rats; D012604:Scorpion Venoms / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology*; D012605:Scorpions / Q000737:chemistry*; D062687:Sodium Channel Agonists; D015222:Sodium Channels / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology; D014701:Veratridine / Q000494:pharmacology
D007328:Insulin; D009498:Neurotoxins; D012604:Scorpion Venoms; D062687:Sodium Channel Agonists; D015222:Sodium Channels; C119038:Ts-gamma neurotoxin; C093268:tityustoxin V; D013779:Tetrodotoxin; D014701:Veratridine; D005947:Glucose