Tityus? toxin, a high affinity effector of the Na+ channel in muscle, with a selectivity for channels in the surface membrane

Abstract

Toxin γ from the venom ofTityus serrulatus scorpion produces a partial block of the surface Na⁺ channel in frog muscle. This block occurs with no change in the voltage-dependence or in the kinetics of the remaining surface Na⁺ current. The partial blockade of Na⁺ channel activity occurs with no change in tubular Na⁺ currents nor in twitch tension. The maximum effect of the toxin is attained at concentrations as low as 3×10⁻¹⁰ M. Hyperpolarization to potentials more negative than the resting potential (E=−90 mV) reduces or abolishes the effect of the toxin. Radioiodinated toxin γ binds to frog muscle membranes with a very high affinity corresponding to a dissociation constant of about 1×10⁻¹¹ M. Data obtained with both rabbit and frog muscle indicate that toxin γ is specific for Na⁺ channels in surface membranes. Toxin γ does not seem to bind to Na⁺ channels in T-tubule membranes. The biochemical data are in good agreement with electrophysiological studies and data on contraction. There is oneTityus γ toxin binding site per tetrodotoxin binding site in surface membranes. Competition experiments have confirmed thatTityus γ toxin binds to a new toxin receptor site on the Na⁺ channel structure. This site is the same that the toxin II fromCentruroides suffusus binding site, but this toxin has 100 times less affinity for the Na⁺ channel thanTityus γ toxin.