How would the massive release of acetylcholine impact skeletal muscles?
The correct answer and explanation is:
Answer:
A massive release of acetylcholine (ACh) at the neuromuscular junction would initially cause continuous and excessive stimulation of skeletal muscles, leading to sustained muscle contraction (tetany). However, this overstimulation can quickly lead to muscle fatigue, desensitization of receptors, and eventually muscle paralysis.
Explanation:
Acetylcholine is a neurotransmitter critical for skeletal muscle contraction. It is released by motor neurons at the neuromuscular junction and binds to nicotinic acetylcholine receptors on the muscle fiber’s motor endplate. This binding opens ion channels that allow sodium ions (Na⁺) to flow into the muscle cell, generating an action potential that triggers muscle contraction.
If there is a massive release of acetylcholine:
- Excessive Stimulation:
The large amount of ACh would continuously bind to its receptors, causing prolonged depolarization of the muscle membrane. This results in sustained muscle fiber excitation and contraction (a state called tetany). - Failure to Relax:
Normally, acetylcholine is rapidly broken down by the enzyme acetylcholinesterase in the synaptic cleft, which stops stimulation and allows the muscle to relax. With too much ACh, the breakdown cannot keep up, so the muscle remains contracted. - Receptor Desensitization:
Persistent exposure to high levels of ACh causes nicotinic receptors to become desensitized or inactivated. This means the receptors stop responding to ACh, which eventually prevents further muscle contraction. - Muscle Fatigue and Paralysis:
After sustained contraction and receptor desensitization, the muscle cannot contract anymore, leading to paralysis. This is because the muscle fibers are unable to generate new action potentials despite the presence of ACh. - Clinical Relevance:
This mechanism is seen in conditions such as organophosphate poisoning (e.g., certain pesticides or nerve agents) which inhibit acetylcholinesterase, leading to excessive ACh accumulation. Patients exhibit muscle twitching, cramps, and eventually respiratory muscle paralysis, which can be fatal without treatment.
In summary, a massive release of acetylcholine causes initially excessive and sustained contraction of skeletal muscles, but this is quickly followed by receptor desensitization and muscle paralysis due to failure of normal neuromuscular signaling.