Snake Venoms and the Neuromuscular Junction

Robert L. Lewis, M.D.; Ludwig Gutmann, M.D.

Disclosures

Semin Neurol. 2004;24(2) 

In This Article

Neuromuscular Synaptic Transmission

Neuromuscular synaptic transmission involves several distinct steps and each step is a possible site of action for neurotoxins. Acetylcholine is the neurotransmitter utilized for neuromuscular transmission and is synthesized from inactive precursors within the presynaptic nerve terminal.[9] Following synthesis, acetylcholine is packaged in small vesicles within the nerve terminal cytoplasm and then released in response to an action potential. When the action potential arrives at the nerve terminal, voltage gated Ca2+ channels are opened and Ca2+ moves down its electrochemical gradient into the nerve terminal. The elevation of unbound Ca2+ leads to fusion of the vesicles with the presynaptic membrane. Acetylcholine is released into the synaptic cleft and combines with acetylcholine receptors on the postsynaptic membrane. This opens ion channels in the post-synaptic membrane, which permit the flow of positive-charged ions down their concentration gradient and depolarization of the postsynaptic membrane. If the response reaches threshold, a regenerative action potential is generated on the postsynaptic membrane, which ultimately results in muscle contraction. The action of the acetylcholine is terminated rapidly by the enzyme acetylcholinesterase, and the process repeats.[9,13]

Effects of neurotoxins are manifested as interference of neuromuscular signal transmission and can vary from subtle alterations of neurotransmitter release to complete neuromuscular block. The activity of neurotoxins can be exerted at the presynaptic elements, post-synaptic elements or both.[14] Most snake venoms contain toxins that affect both.[7]

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