Modification of Na channel gating by an α scorpion toxin from Tityus serrulatus

• Published in: The Journal of general physiology Vol. 93; no. 1; pp. 67 - 83
• Main Authors: KIRSCH, G. E, SKATTEBØL, A, POSSANI, L. D, BROWN, A. M
• Format: Journal Article
• Language: English
• Published: New York, NY Rockefeller University Press 1989; The Rockefeller University Press
• Subjects: Animals; Arachnida; Biochemistry. Physiology. Immunology; Biological and medical sciences; Buthidae; Cells, Cultured; Cerebral Cortex - cytology; Electrophysiology; Fundamental and applied biological sciences. Psychology; Invertebrates; Mice; Muscles - cytology; Myocardium - cytology; Neuroblastoma - physiopathology; Neurons - cytology; Neurotoxins - pharmacology; Physiology. Development; Rats; Scorpion Venoms - pharmacology; Sodium Channels - drug effects; Sodium Channels - physiology; Cell culture; Scorpionides; Electrophysiology; Ionic channel; Ionic current; Neuroblastoma; In vitro; Toxin; Arachnida; Sodium; Arthropoda; Invertebrata; Membrane channel; Scorpionidae; Gating
• ISSN: 0022-1295; 1540-7748
• DOI: 10.1085/jgp.93.1.67

The effects of TsIV-5, a toxin isolated from the Brazilian scorpion Tityus serrulatus, on whole-cell and single-channel Na currents were determined in N18 neuroblastoma cells. In whole-cell records at a test potential of -10 mV, external application of 500 nM TsIV-5 slowed inactivation 20-fold and increased peak current by about one-third without changing time-to-peak. Both the steady-state activation and inactivation curves were shifted to more negative potentials. Other alpha scorpion toxins produce similar effects but the single-channel mechanism is not known. TsIV-5 caused a voltage-dependent prolongation of mean single-channel open time such that at a test potential of -60 mV no change was observed, whereas at -20 mV mean open time increased about threefold and prolonged bursting was observed. Macroscopic current reconstructed from summed single-channel records showed a characteristic toxin-induced potentiation of peak current and a 20-fold slowing of the decay phase. TsIV-5 does not discriminate between tissue-specific Na channel subtypes. Prolonged open times and bursting were also observed in toxin-treated Na channels from rat ventricular myocytes, rat cortical neurons, and mouse skeletal muscle. The toxin effects are shown to be consistent with a kinetic model in which TsIV-5 selectively interferes with the ability of the channel to reach the inactivated state.