Voltage-dependent displacement of the scorpion toxin Ts3 from sodium channels and its implication on the control of inactivation.
The voltage-dependent displacement of the scorpion Tityus serrulatus alpha-toxin Ts3 was investigated in native sodium channels of GH3 cells by examining the removal of its effects in toxin-free solution. Toxin at saturating concentration was pulsed (approximately 1 s) directly onto the cell, thus causing an eight-fold increase of the slow component (taus = 6 ms) of fast inactivation, and a three-fold increase of the time constant of its fast component. At 0 mV, maximal conductance was achieved in cells before and after treatment with Ts3, and no displacement of the toxin could be detected. Toxin displacement occurred if stronger depolarising pulses (> 100 mV) were applied. The rate of displacement depended on the amplitude and duration of the pulses, and was not related with outward Na+ flux. We propose a model in which activation does not require complete movement of segment S4 of domain IV (IVS4) and that a more extensive movement of this segment is needed for normal fast inactivation. A kinetic model is presented that can account for the typical effects of site 3 toxins.
Campos
Fabiana V
FV
Department of Biochemistry and Immunology, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Caixa Postal 486, 30161-970 Belo Horizonte, MG, Brazil.
Coronas
Fredy I V
FI
Beirão
Paulo S L
PS
D000818:Animals; D015640:Ion Channel Gating; D007700:Kinetics; D009498:Neurotoxins / Q000378:metabolism / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D051381:Rats; D012604:Scorpion Venoms / Q000378:metabolism / Q000494:pharmacology*; D015222:Sodium Channels / Q000502:physiology*; D013997:Time Factors; D014407:Tumor Cells, Cultured
D009498:Neurotoxins; D012604:Scorpion Venoms; D015222:Sodium Channels; C485970:Ts3 toxin, Tityus serrulatus