Two classes of channel-specific toxins from funnel web spider venom.

1. The paralytic effects and neuromuscular actions of Agelenopsis aperta venom on insects were analyzed biochemically and electrophysiologically. 2. Paralysis caused by Agelenopsis venom is correlated with two effects on neuromuscular transmission: postsynaptic inhibition and presynaptic excitation. These effects are explained by the actions of two classes of toxins purified by RPLC, the alpha- and mu-agatoxins. 3. The alpha-agatoxins are low molecular weight, acylpolyamines which cause rapid, reversible paralysis correlated with use-dependent postsynaptic block of EPSPs and ionophoretic glutamate potentials. The mu-agatoxins are cysteine-rich polypeptides which cause irreversible paralysis and repetitive action potentials originating in presynaptic axons or nerve terminals. 4. The joint actions of the alpha- and mu-agatoxins lead to significantly higher rates of paralysis than are obtained by either toxin class alone, and this may relate to enhancement by excitatory mu-agatoxins of use-dependent block caused by alpha-agatoxins.