Neuromuscular Transmission

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)