Question

Poisonous nerve gases such as sarin work by breaking down AChE (acetylcholinesterase) at nerve-muscle synapses. What do you think is the effect of nerve gas on the muscles? Why? Be sure to include a discussion of the steps that occur in the nerve and motor end plate during transmission at the neuromuscular junction and the role of AChE in normal synaptic transmission. Propose a way to counteract the effects of nerve gas (besides getting rid of the gas itself).

Answer 1

Answer 1)

Normally acetycholine around synapse is responsible for contrqction of muscles .
Acetycholine is destroyed by acetycholinesterases into choline and acetate
There are drugs like anticholinesterases which destroy acetycholinesterases and result in accumulation of Acetycholine around synapses( As acetycholine is not destroyed by cholinesterases because of ita destruction by anticholinesterases )

Nerve gases like Sarin are Organophosphate which cause Irreversible inhibition of Anticholinesterases .So accumulation of Acetylcholine occur around synapse .
Acetylcholine is cholinergic drug causing contraction of muscles .

This causes excessive stimulation of muscarinic and nicotinic receptors at the postsynaptic membrane. . Nicotinic effect on skeletal muscle can cause fasciculation and flaccid paralysis of muscles .

.Mechanism is by Acetycholine stimulates the Nicotinic Nm receptors resulting in depolarisation of the membrane .This effect is responsible for initial Fasciculations.This is followed by constant depolarisation of the endplate( because of excess of acetycholine ) making them refractory to other impulses and Muscle relaxation results .It is a type of Flaccid paralysis .

Answer 2)

Steps in Neuromuscular transmission
1.)The action potential travels down the motor neuron and depolarizes the presynaptic membrane.

2)This depolarization opens voltage-gated Ca2+ channels in the presynaptic membrane, resulting in Ca2+ influx into the presynaptic terminal.

3) The rise in Ca2+ causes synaptic vesicles to release Acetylcholine. The amount of neurotransmitter release is directly related to the rise in cytosolic Ca2+, i.e., the more Ca2+ enters , more Acetylcholine released.

4. Ach binds to a nicotinic receptor located on the muscle membrane (NM receptor). The NM receptor is a non-selective monovalent cation channel (both Na+ and K+ can move). Now Na+ has a much greater net force depolarization occurs. This depolarization is called an end-plate potential (EPP). The magnitude of the EPP is directly related to the amount of Ach released.

5. The resulting depolarization opens fast Na+ channels on the muscle membrane (sarcolemma) causing an action potential to occur in the sarcolemma. An action potential in the motor neuron cause release of enough Ach to cause End Plate Potential that is at least threshold for the action potential in the skeletal muscle cell which occurs under normal circumstances . There is a one-to-one relationship between an action potential in the motor neuron and an action potential in the skeletal muscle cell.

6. The actions of Ach are terminated by acetylcholinesterase (AchE), that breaks Acetylcholine into choline and acetate.
Acetylcholinesterase located on postsynaptic membrane . Choline is taken back into the presynaptic terminal (reuptake), hence providing substrate for re-synthesis of Acetycholine

Answer 3)Protection from nerve gases
**First decontaminate from places and wash the skin with soap and water .

*Flush the mouth and eyes with water .

**If there is respiratory weakness involved then immediately apply Oxygen

**Drugs like Atropine is antidote for sarin gases poisoining .( Atropine is anticholinergic drug destroy acetycholine)

**Others Enzyme reactivators like Pralidoxime ,Obidoxime and Diacetylmonoxime can be used to regenerate acetycholinesterase in Organophospahte poisoning .

**Principle indications of Oximes are Resoiratory depression and muscle weakness .