Several protein neurotoxins from a variety of animals are known to increase the release of acetylcholine at the neuromuscular junction. Some toxins stimulate release in an uncontrolled fashion by inducing depolarization of the nerve terminal. Such toxins include those that alter the activation and inactivation characteristics of sodium channels, and those that create transmembrane pores. Toxins that facilitate evoked neurotransmitter release are more interesting because they can be used to explore the normal control mechanisms that modulate physiologically relevant release. Several snake toxins with phospholipase activity can block release, although they initially cause a stimulation. These include β-bungarotoxin, crotoxin, notexin, and taipoxin. The facilitation of transmitter release in mammalian nerve-muscle preparations is associated with a blockade of some of the potassium channels of the nerve terminal. This will slow the repolarization after an action potential, and thus allow calcium ions longer to enter the terminal and trigger release. Another type of facilitatory toxin is dendrotoxin from mamba snakes. It also blocks potassium channels, although a different subtype to those affected by the phospholipase toxins. Dendrotoxin causes repetitive firing of nerve terminals in addition to increasing acetylcholine release. More recently, the scorpion toxin, noxiustoxin, has been demonstrated to act prejunctionally to increase transmitter release. Another toxin with the potential to affect transmitter release is charybdotoxin, which blocks some potassium channels that are activated by internal calcium ions. Although charybdotoxin blocks calcium-activated potassium currents at motor nerve terminals, this does not normally affect acetylcholine release unless there is simultaneous block of voltage-dependent potassium currents.
- transmitter release