Download Effect of Ach on Sk Ms

Dose response curve of Ach & the effect of different
drugs on the isolated frog rectus abdominis
Lab # 5
Objectives
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Describe frog rectus abdominis
Discuss neuromuscular transmission
Compare NN R with NM R
Explain drugs act on neuromuscular transmission
Frog Rectus Abdominis
Description:
-
It is a skeletal, voluntary, striated & transverse muscle
It receives somatic motor innervation
The transmission is mediated through release of Ach that acts on Nm Rs
present postsynaptically on the muscle
Neuromuscular(myoneural)
junction
CNS
Voluntary motor nerve
Nm R
Neuromuscular transmission
Neuromuscular transmission
1- Action potential propagation through nerve fiber
2- Calcium influx into the nerve ending
3- Release of Ach from its vesicles (fusion with membrane &
exocytosis)
4- Release of Ach into synaptic cleft
5- Ach binds to Nm R postsynaptically
6- Activation of Na-K channels→ Na influx; contraction
7- Ach action is terminated by cholinesterase enzyme
Illustration of neuromuscular transmission
*flash2
Comparison between Nn & Nm
Nn
Nm
smooth muscle
skeletal muscle
Located in ganglia
Located
postsynaptically(MEP)
Drugs that affect skeletal muscles
1- Centrally acting drugs
e.g. Diazepam (skeletal ms. relaxant)
2- Peripherally acting drugs
a- Presynaptically (motor nerve)
b- Postsynaptically (sk.ms.)
Drugs that affect skeletal muscles; cont.
Presynaptically acting drugs
1- ↓ AP propagation
e.g. local anesthetics
2- ↓ Ach synthesis
e.g. hemicholinium, vesamicol
3- ↓ Ach release
e.g. botulinum toxin
4- ↓ calcium conc.
e.g. Magnesium
Drugs that affect skeletal muscles; cont.
Postsynaptically acting drugs
A-Drugs that decrease transmission
B-Drugs that increase transmission
Drugs that affect skeletal muscles; cont.
Drugs that decrease transmission
Non-depolarizing
(Competitive)
Depolarizing
(noncompetitive)
MOA
Competing with Ach at
NmR
Excessive
depolarization→
transmission failure &R
blockage
Examples
Tubocurarine
Gallamine
Succinylcholine
Decamethonium
Type of paralysis
produced
Flaccid
Spastic
Drugs that affect skeletal muscles; cont.
Drugs that increase transmission
Cholinesterase inhibitors
A- Reversible
e.g. neostigmine, physiostigmine
B- Irreversible
e.g. organophosphorus insecticides
* Both will lead to accumulation of Ach at myoneural junction
PART 1
PART 2
A
W N
Ach
0.05ml
Height = A-B
Curves
W+N
W+N
Ach 0.1ml
0.2ml
Ach
W+N
0.4ml
Ach
W+N
N
0.1ml
Ach
W+N
0.1ml
Ach
W+N
0.1ml
Ach
Curare 0.2ml
B
Physiostegmine
0.1ml
N
0.1ml
Ach
Curves
On semi-log paper
Ht.
Ht.
*
*
On normal paper
*
Dose
Dose