This is a real-world medical entrance exam question, please give the true answer based on the question and selection. Topic name: None, Subject name: Anaesthesia
Mechanism of action of curare is ? 
Select and explain. 
A. Reducing end plate potential, B. Reducing presynaptic potential, C. Inhibits K+ channels, D. Inhibits Na+ channels
A: Reducing end plate potential
Answer: A: Reducing end plate potential 
Explanation: Ans. is 'a' i.e., Reducing end plate potential Curare (D-tubocurarine) is a competitive neuromuscular blocker. All neuromuscular blockers bind to Nm receptors on end-plate and prevents generation of end-plate potential. Mechanism of action of muscle relaxants To know the mechanism of action of different skeletal muscle relaxants one should know the normal sequences of events in contraction and relaxation of skeletal muscle ? A. Contraction There is discharge of motor neuron. Release of Ach at neuromuscular junction. Binding of Ach to nicotinic (NM) cholinergic receptors at end plate. Binding of Ach to nicotinic receptors causes opening of Na.* channels (NM receptor has intrinsic ion channel). Opening of Na+channel generate end plate potential on skeletal muscle membrane. If end plate potential is above a threshold level, action potential is generated on skeletal muscle membrane- depolarization. Depolarization of skeletal muscle membrane causes intracellular release of Ca" from sarcoplasmic reticulum. Ca" binds to troponin 'c', uncovering myosin binding site of actin. Cross linking between actin and myosin, and sliding of thin filaments on thick filaments - contraction. B. Relaxation Ca" pumped back into sarcoplasmic reticulum. Release of Ca" from Troponin. Cessation of interaction between actin and myosin - relaxation. Now coming back to the mechanism of different skeletal muscle relaxants. Competitive (nondepolarising) blockers The competitive blockers have affinity for N. receptors but no intrinsic activity. They compete with Ach for N receptor --) called competitive blockers. They prevent binding of Ach to N. receptors- No opening of Na- channels - No depolarization, so these are called non-depolarizing blockers. Competitive blockers reduce the frequency of channel opening but not its duration or the conductance of a channel once it has opened. When the magnitude of end plate potential falls below a critical level, it is unable to trigger propagated muscle action potential muscle fails to contract. Neostigmine (anticholinesterases) antagonises competitive blockers. Depolarizing blockers Depolarizing blockers have affinity as well as submaximal intrinsic activity on A r receptors. They depolarize muscle end plates by opening of Na+ channels and initially produce twitching and fasciculations (not full contraction as these drugs have submaximal activity)-o, they are called depolarizing blocker. These drugs do not dissociate rapidly from the receptor (NM) - Persistant paial depolarization- Na+ channels get inactivated - flaccid paralysis. Neostigmine does not antagonise depolarising blockers. Under ceain conditions depolarizing agents produce dual mechanism of neuromuscular blockade which can be divided into two phases : a. Phase I block Rapid in onset Result from persistant depolarization of muscle end plate. Has classical features of depolarization block. Block is not antogonized by anticholinesterases (neostigmine). b. Phase H block Slow in onset Results from desensitization of receptor to ACh. Resembles block produced by competitive blockers. Block is paially reversed by anticholinesterases (Neostigmine). In man normally only phase I block is seen typical depolarizing block. Phase II block is seen when fluorinated anaesthetics have been given or when SCh is injected in high dose. SCh also produces phase II block in patients with atypical or deficient pseudocholinesterase.