This document discusses neuromuscular transmission and excitation-contraction coupling at the neuromuscular junction (NMJ). It describes the secretion of acetylcholine (Ach) from nerve terminals, how Ach opens ion channels on the postsynaptic membrane, and how this leads to end plate potentials and excitation of skeletal muscle fibers. The document also discusses Ach formation and release, safety factors at the NMJ, fatigue of the NMJ, and the molecular mechanisms of excitation-contraction coupling in skeletal muscle.

1. DR.MUMTAZ ALI NAREJO
KHAIRPUR MEDICAL COLLEGE
SINDH PAKISTAN

2. Aims
 Neuromuscular transmission
 Excitation-contraction coupling
 Motor end plate-NMJ
 Secretion of Ach from nerve terminal
 Ach open channel on postsynaptic membrane
 Destruction of Ach by acetylcholinestrase
 Safety factor and fatigue of NMJ
 Molecular biology of Ach formation and release
 Transverse T-tubule-sarcoplasmic reticulum system

3. NMJ
 Transmission of impulses=>
Nerve endings =>
Skeletal muscle fibre=> NMJ
 Motor endplate
 Presynaptic membrane
 Syaptic space/cleft
 Postsynaptic membrane
 Synaptic trough/gutter
 Subneural cleft:inc surface
area
 Axon terminal : ATP
 Ach
 Synaptic vesicle
 Acetylcholinesterase

6. Secretion of Ach from nerve
terminal
 Nerve impulse=>NMJ
 125 vesicle
 Dense bar
 voltage gated Ca++
 Synaptic space=>nerve terminal
 Calmodulin dependent
protein kinase
 P+synapsin protein
 Anchor vesicle
 Active zone
 Dock at release site
 Fuse with neural membrane
 Empty Ach
 exocytosis

7. Ach opens ions channels on
postsynaptic membrane
 Ach receptors
 Ach gated ion chanel:0.65nm
 Mouth of subneural cleft
 Ach receptor :275000
 Fetal :2 alpha,beta,delta,gama
 Adult:2alpha,beta,delta,epsilon
 Close
 Open =2 ach+2alpha
 Na+,K+,Ca++
 Patch clamp study
 15000-30,000 Na+ ms
 Endplate potential
 Acetylcholineseterase

8. End plate potential & excitation of
skeletal muscle
 Curare :
block Ach
 Botulinum toxin:
dec release of Ach
from nerve terminal
Safety factor :1 impulse
3 enplate potentials
Fatigue of NMJ :
100/sec=>diminish Ach

9. Ach formation & release
 Golgi apparatus =>small vesicles(40nm)=>axoplasm=>300000
small vesicle=>nerve terminal
 Ach synthesized in nerve terminal=>10,000 Ach=>small vesicle
 A.P=>N.T=>Ca++=>125 Ach vesicle fusion e N.T membrane
=>exocytosis=>Ach=>Acetate +choline
 Drugs have Ach action:methacholine,carbachol,nicotine
 Inactivate Achesterase:
neostigmine,physiostigmine,diisopropylflorophosphate
 Block NMJ:curare:atracurium
 Mysthenia gravis=>muscle weakness=>autoantibodies =>Ach rec

10. Excitation-contraction coupling
 RMP: -80-90mv
 Duration AP:1-5ms
 Velocity:3-5m/s
 Spreads:T-tubule
 Ca++: release
 E-C coupling
 S.R: cisterne
longitudinal channel
 Dihydropyridone R
 Ca++(raynodine R)

15. Refrences
 Gyton text book of physiology
 Netter atlas of physiology

16. THANKYOU