Modification of Na channel gating by an alpha scorpion toxin from Tityus serrulatus.
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.
Kirsch
G E
GE
Department of Physiology and Molecular Biophysics, Baylor College of Medicine, Houston, Texas 77030.
Skattebøl
A
A
Possani
L D
LD
Brown
A M
AM
D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D004594:Electrophysiology; D051379:Mice; D009132:Muscles / Q000166:cytology; D009206:Myocardium / Q000166:cytology; D009447:Neuroblastoma / Q000503:physiopathology*; D009474:Neurons / Q000166:cytology; D009498:Neurotoxins / Q000494:pharmacology*; D051381:Rats; D012604:Scorpion Venoms / Q000494:pharmacology*; D015222:Sodium Channels / Q000187:drug effects* / Q000502:physiology
D009498:Neurotoxins; D012604:Scorpion Venoms; D015222:Sodium Channels; C003609:tityustoxin