Abstract

The combined effects of batrachotoxin (BTX) and either scorpion (Leiurus quinquestriatus quinquestriatus) venom (LqqV) or alpha-scorpion toxin (alpha-LqqTX) purified from LqqV on single voltage-gated Na channels were studied in planar lipid bilayers. In the presence of BTX, LqqV caused the channels to remain open at membrane potentials at least 50 mV more hyperpolarized than with BTX alone. alpha-LqqTX mimicked the effect of LqqV, suggesting that this toxin is the active component of the venom. LqqV did not significantly alter single-channel conductance, voltage-dependent block by saxitoxin, or voltage-dependent block by Ca2+, indicating that the venom preferentially affects gating rather than ion permeation. The results indicate that a cooperative interaction between alpha-LqqTX and BTX strongly favors the open state of the Na channel by causing a large hyperpolarizing shift in the voltage dependence of activation. This effect on activation gating is not predicted from the individual effects of the toxins.