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NEUROMUSCULAR TRANSMISSION
OBJECTIVES
Examine the structure of a neuromuscular junction
Understand the sequence of events at the Neuromuscular – junction following a stimulus
What you need to know: Anatomy of a skeletal muscle
cell Resting membrane potential Action potential Depolarization
Overview: Skeletal muscle contraction
Stimulated by a nerve ending
Electrical current / action potential
Rise in intracellular calcium
Muscle contraction* excitation-contraction coupling
Muscle sarcolemma
Anatomy of a Skeletal Muscle and Nerve Ending ( gross microscopic)
The neuromuscular Junction and the Nerve Stimulus
Steps in Acetylcholine synthesis Degradation
Steps: 1. Synthesis choline + Acetyl-co-A * Choline Acetyl Transferase
2. storage
3. release
4. Binding of Ach to receptors•EPP•MEPP
5. Degradation choline + Acetate ion* acetylcholinesterase
6. Recycling of cholineCholine – reabsorbed back to the axonal terminal>300,000 vesicles/axonal terminal1,000 – 50,000 Ach Molecules/Vesicle
DRUGS AFFECTING N-M JUNCTION TRANSMISSIONDrugs that inhibit choline transport to the nerve axon
Hemicholinium
Drugs that block release of Ach at the presynaptic membraneBOTULINUM TOXINBLACKWIDOW SPIDER VENOM“OPPOSITE”
Drugs that stimulate the mucle fiber with Ach-like actionCARBACHOL, METACHOLINE, NICOTINE
DRUGS THAT BLOCK TRANSMISSION AT THE N-M JUNCTION
Neuromuscular Blocking Agent1.Nondepolarizing : Curare, Pancuronium, Tracium
2. Depolarizingsuccinylcholine
DRUGS THAT STIMULATE N-M-J BY INACTIVATING ACETYLCHOLINESTERASE
(anti-chease)
1.Reversible type (temporarily binds)Physostigmine, NeostigmineTx: myasthenia Gravis
DRUGS THAT STIMULATE N-M-J BY INACTIVATING ACETYLCHOLINESTERASE
(anti-chease)
2. Irreversible typeIsoflurophate (Di- isopropyl flourophosphate)-Aging*chemical activatorsPRALIDOXIME ( PAM)