1. Sarin is a synthetic, volatile neurotoxin that can enter the body through the

Question

1. Sarin is a synthetic, volatile neurotoxin that can enter the body through the eyes, skin, lungs, and Gl tract. Early symptoms of sarin exposure include watery eyes and constricted pupils. Later, more severe symptoms include skeletal muscle paralysis and difficulty breathing. If not treated, paralysis of respiratory muscles leads to death. a) Does sarin affect effectors of the somatic nervous system, autonomic nervous system, neither, or both? Explain. (2 pts) b) Briefly describe the mechanism of action of sarin. (3 pts) c) Explain how sarin causes each: watery eyes, constricted pupils. (4 pts) d) Explain how sarin affects the movement of Nat into a skeletal muscle cell. (2 pts) e) Explain how sarin affects the concentration of Ca2+ in the cytosol of a skeletal muscle cell. (2 pts) f) In a myofibril, how would sarin affect the position of thin filaments relative to thick filaments? Explain. (2 pts) 2. Describe the changes that occur within the left ventricle throughout the course of the cardiac cycle, including changes in (a) pressure, (b) volume, (c) position of the left AV valve (bicuspid), and (d) the aortic semilunar valve. Begin at the onset diastole (relaxation period). (5 pts)

Explanation / Answer

1a.When our nerves start to communicate with each other internally, they release chemicals called neurotransmitters.The amount of the neurotransmitters in our body helps determine whether a nerve is fired or not.The nerve agents alter the neurotransmitters and the go signalling between our nerves, telling them what do to on a normal basis. When that frequency is altered, which affects the neurotransmitter acetylcholine, sarin attacks both the nervous systems by interfering with the degradation of the neurotransmitter acetylcholine at neuromuscular junctions.

1b. Mechanism -
Specifically, sarin is a potent inhibitor of acetylcholinesterase, an enzyme that degrades the neurotransmitter acetylcholine after it is released into the synaptic cleft. In vertebrates, acetylcholine is the neurotransmitter used at the neuromuscular junction, where signals are transmitted between neurons from the central nervous systems to muscle fibres. Normally, acetylcholine is released from the neuron to stimulate the muscle, after which it is degraded by acetylcholinesterase, allowing the muscle to relax. A build-up of acetylcholine in the synaptic cleft,
due to the inhibition of cholinesterase, means the neurotransmitter continues to act on the muscle fibre so
that any nerve impulses are effectively continually transmitted.Sarin acts on cholinesterase by forming a covalent bond with the particular serine residue at the active site. Fluoride is the leaving group, and the resulting phosphoester is robust and biologically inactive.Its mechanism of action resembles that of some commonly used insecticides, such as malathion. In terms of biological activity, it resembles carbamate insecticides,
such as Sevin, and the medicines pyridostigmine, neostigmine, and physostigmine.

1c)i-After a neurotransmitter has delivered a message, an enzyme usually comes along and demolishes it.But there's always a nerve agent which blocks those enzymes. The enzyme cant breaks down the neurotransmitter, so the neurotransmitter stays around and keeps giving its message.For example, if the message released a little
water into the eye, the now repeated message becomes "make your eyes water uncontrollably.

1c)ii- Sarin the drug acts on a parasympathetic nervous system which thus causes the constriction of the pupil

1d) Sarin is a gaseous organophosphate compound that is commonly used in chemical warfare, as it is a powerful nerve agent that can cause death to those who inhale the gas within minutes. Sarin is an irreversible inhibitor of the enzyme acetylcholinesterase, an enzyme that catalyzes the breakdown of the acetylcholine neurotransmitter
into acetate and choline.The excess Ach would continually stimulate Cholinergic receptors and make the ion channels opened to be invaded by Na+ ions. This will depolarize the membrane and will
send a continuous signal.

1e) The DHSR would be continually stimulated by the continuous electrical signal, and thus the Ryanodine receptor also. This will open the Calcium channels allowing them to continually bind to troponin.The heads of the myosin are allowed to form cross-bridges causing shortening of the sarcomere, power strokes and leading to contraction and constriction.All this is allowed because Ca2+ binds to troponin which moves the tropomyosin and exposes the G sites on the actin

1f) Sarin the drug causes disorganised secretions of the motor neurons, these neurons release neurotransmitters such as acetylcholine which is responsible for muscular contraction. The contraction takes place when the thin filaments move and hence it would probably affect the position of the thin filaments more than the thick filaments

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