Voltage-dependent effect of a scorpion toxin on sodium current inactivation

Abstract

• 1. In voltage clamped nodes of Ranvier inactivation of the sodium permeability is slowed by toxin V from the scorpionCentruroides sculpturatus, by sea anemone toxin ATX II or by internally applied KIO₃. The slow decay of the Na inward current is markedly accelerated if the test pulse is preceded by a depolarizing conditioning pulse followed by a 10–500 ms pause. This phenomenon was studied in detail, using conditioning pulses of varying amplitude and up to 15 s duration.

• 2. In nodes treated with toxin V a 20 ms conditioning pulse to positive potentials was sufficient to produce a clear acceleration of the decay of the Na current and a reduction of the inward current remaining at the end of a 50 ms test pulse, i.e. a weakening of the toxin effect. In nodes treated with ATX II or internal KIO₃ longer conditioning pulses were required. A similar effect of conditioning pulses on the decaying phase of the Na current was also observed in untreated fibres.

• 3. To study the phenomenon quantitatively we fitted the decaying phase of the inward Na current with the equationI _Na=A exp(-t/τ₁)+B exp(-t/τ₂)+C The effect of depolarizing conditioning pulses could be described as an increase of A, a decrease of B and C and a reduction of the time constants τ₁ and τ₁.

• 4. I ₅₀/I _peak, the normalised inward current remaining at the end of a 50 ms test pulse, decreased exponentially with increasing duration of the conditioning pulse to a steady-state value. The time constant τ and the steady-state value depended on the potential during the conditioning pulse. For nodes treated with toxin V, τ was 0.24 s at 0 mV and 12° C and half inhibition occurred at −42 mV. The time constant τ was larger for nodes treated with ATX II or internal KIO₃. At positive potentials, I₅₀ was reduced to 20% of the control value in toxin V-treated nodes, but only to 70% in KIO₃-treated nodes.

• 5. Recovery from the effect of the conditioning pulse was studied by varying the pause between conditioning pulse and test pulse; recovery was 66–100% complete after 500 ms.

• 6. The results are interpreted by assuming that a sepolarizing conditioning pulse (a) accelerates inactivation of the sodium permeability and (b) causes dissociation of the toxin-receptor complex or transition into an inactive state. The latter effect occurs in toxin V-treated fibres but not in those treated with ATX II or KIO₃.