Toxins and the Neuromuscular System Edoxie E

Home , Botulinum toxin, Repolarization

ORGANISATION FOR THE PROHIBITION OF CHEMICAL WEAPONS Working Together for a World Free of Chemical Weapons Toxins and the Neuromuscular System Edoxie E. Allier-Gagneur, Wesam S. Alwan and Jonathan E. Forman

A synapse, the gap between two nerve cells (neurons), allows chemical signals to be Na+ channels close K+ channels open relayed from one neuron to another. The junction between a motor neuron and a muscle is referred to as a neuromuscular synapse. Neurons rely on the movement of ions (charged Repolarization + 2+ - + species especially K , Ca , Cl , Na ) inducing a current, the so-called action Depolarization potential responsible for electrical signalling. Signals are initiated when a neurotransmitter K+ channels close

+ chemical (acetylcholine) binds to a speciﬁc receptor (acetylcholine receptor), Na channels open Hyperpolarization triggering the opening of an ion channel. Information is transmitted along the Time neuron, employing a signaling system similar to Morse code. Action Potential Mechanism

Muscle fiber Tetraethylammonium

Curare Blocks the K+ ion channel preventing propagation of the signal. LD = 6.5 x 107 ng/kg 50 T-Tubuli Sarcolemma

Inhibits the acetylcholine receptor, Presynaptic neuron resulting in paralysis.

5 Bungarotoxin β LD50= 5 x 10 ng/kg

Synapse

Induces excessive neurotransmitter release, resulting in excessive muscle contraction. Botulinum Toxin

4 LD50= 8 x 10 ng/kg

Anatoxin Postsynaptic Prevents the fusion of vesicles to the pre-synaptic membrane. This neuron prevents acetylcholine from entering the synapse, inducing paralysis.

LD50=1ng/kg Binds to neurotransmitter receptors, inducing excessive muscle contraction.

4 LD50= 5 x 10 ng/kg Saxitoxin

Vesicles

Neurotransmitter Receptors

Acetylcholine (Neurotransmitter) Blocks voltage-gated Na+ channels, preventing depolarization.This Potassium (K+) Channels results in paralysis. LD = 1 x 104 ng/kg Sodium (Na+) Channels 50

Point of initiation of toxin eﬀect Once a signal is released into the sarcolemma (a sheath surrounding the muscle), an action potential travels down the T-Tubuli ( structure found between muscle ﬁbers). This triggers a release of calcium ions into the sarcoplastic reticulum which results @opcw @opcw_st /opcwonline /opcwonline /company/opcw /opcw in muscle contraction. For more information, scan the QR code.