Batrachotoxin under certain conditions has a strong depolarizing effect on the innervated membrane of the monocellular electroplax preparation from the electric eel, Electrophorus electricus. No effect is observed when the toxin (50-200 nM) is applied to the resting membrane for periods up to 1 hr. However, if the membrane is exposed to batrachotoxin and the cell is subjected to stimulation at a stimulus voltage slightly above the threshold for action potential firing, a progressive prolongation of the action potential and concomitant progressive depolarization of the innervated membrane is observed. When the membrane is depolarized by 15-20 mV, a further abrupt all-or-none depolarization occurs, and the potential attains a steady-state value between 0 and -10 mV. Brief stimulation of a cell in the presence of batrachotoxin is sufficient to define a batrachotoxin-treated cell, even though negligible depolarization occurs. If depolarizing agents such as carbamoylcholine or potassium chloride are introduced to such a cell in concentrations that normally produce a 20-30 mV depolarization, the abrupt all-or-none depolarization immediately occurs. All-or-none depolarizations arising from either electrical stimulation or depolarizing agents are unaffected by d-tubocurarine but are completely reversed by tetrodotoxin. Batrachotoxin thus appears to activate only the action potential sodium channels. In the batrachotoxin-treated membrane, these channels can attain stable steady states in either a closed configuration at the normal resting potential or in an open configuration after complete depolarization. A striking hysteresis cycle thus can be generated, which is strongly indicative of a voltage-dependent interaction of the toxin with the action potential sodium channels.

Histrionicotoxin (HTX) at low concentrations of 5-10 microM blocks the postsynaptic potential of the electroplax of Electrophorus electricus. At 100-fold higher concentrations, HTX blocks the directly evoked action potentials of the conducting membrane. The pH dependence of the blockade by HTX at synaptic channels is different from that at the conducting membrane. At the synapse HTX is more potent at acid pH, while at the conducting membrane it is more potent at basic pH. HTX at high concentrations antagonizes the effects of batrachotoxin, indicative of an effect on the batrachotoxin-sensitive sodium channels involved in action potential generation. While the effects of HTX on the synaptic channels are concentration, time, and pH dependent, the effects on the channels of the conducting membrane are, in addition, use dependent, suggesting interactions of HTX with the activated forms of these channels.