Question

A researcher administers sarin, which is known to block the effects of acetylcholinesterase. How would this affect the following?:

A. Acetylcholine levels in the synaptic cleft?

B. Acetylcholine levels in the presynaptic terminal?

C. Acetylcholine levels in the postsynaptic cell?

Answer 1

Sarin [(CH3)2CHO]CH3P(O)F], is a nerve gas that can cause death by inhalation. It inhibits the acetylcholinesterase that breaks down of the acetylcholine neurotransmitter into acetate and choline. Hence, muscle contraction is inhibited. Sarin forms a covalent bond with the serine residue at the active site on the cholinesterase molecule. Hence, the enzyme cannot bind to acetylcholine. After Ach is released, it binds to its receptors on the postsynaptic cell, and induces a cascade of events that culminate in muscle contraction.

A. When a nerve impulse in the presynaptic neuron reaches the synapse, acetylcholine is release in the synaptic cleft. Sarin, therefore increases acetylcholine levels in the synaptic cleft.

B. Acetylcholine is released from the presynaptic terminal. However, since sarin only affects the synaptic cleft, the acetylcholine levels in the presynaptic terminal will not change as it is not affected. Sarin only affects acetylcholine levels after its release from presynaptic terminal.

C. The postsynaptic action of acetylcholine at many cholinergic synapses are terminated by acetylcholinesterase (AChE). The postsynaptic terminal in the postsynaptic cell have a high-affinity, Na+-choline transporter. This transporter takes up the choline produced by ACh hydrolysis. As acetylcholine is not cleaved by AChE, choline is not generated. The postsynaptic cell depolarizes and becomes refractory to subsequent ACh release, causing neuromuscular paralysis. Hence, initially levels of ACh will increase in the postsynaptic cell, but after some time, the levels will remain stagnant, as all the membrane receptors will be completely bound by ACh.