Dose response curve of Ach & the effect of Dose response curve of Ach & the effect of different drugs on the isolated frog rectus different drugs on the isolated frog rectus

abdominisabdominis

Lab # 5Lab # 5

ObjectivesObjectives Describe frog rectus abdominisDescribe frog rectus abdominis Discuss neuromuscular transmissionDiscuss neuromuscular transmission Compare NCompare NNN R with N R with NM M RR Explain drugs act on neuromuscular transmissionExplain drugs act on neuromuscular transmission

Frog Rectus AbdominisFrog Rectus Abdominis

Description:Description:- It is a skeletal, voluntary, striated & transverse muscleIt is a skeletal, voluntary, striated & transverse muscle- It receives somatic motor innervationIt receives somatic motor innervation- The transmission is mediated through release of Ach that acts on The transmission is mediated through release of Ach that acts on

Nm Rs present postsynaptically on the muscle Nm Rs present postsynaptically on the muscle

CNS

Voluntary motor nerve

Nm R

Neuromuscular(myoneural)junction

Neuromuscular transmissionNeuromuscular transmission

Neuromuscular transmissionNeuromuscular transmission

1- Action potential propagation through nerve fiber1- Action potential propagation through nerve fiber2- Calcium influx into the nerve ending2- Calcium influx into the nerve ending3- Release of Ach from its vesicles (fusion with membrane & 3- Release of Ach from its vesicles (fusion with membrane &

exocytosis)exocytosis)4- Release of Ach into synaptic cleft 4- Release of Ach into synaptic cleft 5- Ach binds to Nm R postsynaptically5- Ach binds to Nm R postsynaptically6- Activation of Na-K channels→ Na influx; contraction 6- Activation of Na-K channels→ Na influx; contraction 7- Ach action is terminated by cholinesterase enzyme7- Ach action is terminated by cholinesterase enzyme

flash2flash2

Illustration of neuromuscular transmission

Comparison between Nn & NmComparison between Nn & Nm

NnNn NmNm smooth musclesmooth muscle skeletal muscleskeletal muscle

Located in Located in gangliaganglia

Located Located postsynaptically(MEpostsynaptically(ME

P)P)

Drugs that affect skeletal musclesDrugs that affect skeletal muscles

1- Centrally acting drugs1- Centrally acting drugs

e.g. Diazepam (skeletal ms. relaxant)e.g. Diazepam (skeletal ms. relaxant)

2- Peripherally acting drugs2- Peripherally acting drugs

a- Presynaptically (motor nerve)a- Presynaptically (motor nerve)

b- Postsynaptically (sk.ms.)b- Postsynaptically (sk.ms.)

Drugs that affect skeletal muscles; cont.Drugs that affect skeletal muscles; cont.

Presynaptically acting drugsPresynaptically acting drugs1- ↓ AP propagation1- ↓ AP propagation

e.g. local anestheticse.g. local anesthetics

2- ↓ Ach synthesis 2- ↓ Ach synthesis

e.g. hemicholinium, vesamicole.g. hemicholinium, vesamicol

3- ↓ Ach release3- ↓ Ach release

e.g. botulinum toxine.g. botulinum toxin

4- ↓ calcium conc.4- ↓ calcium conc.

e.g. Magnesium e.g. Magnesium

Drugs that affect skeletal muscles; cont.Drugs that affect skeletal muscles; cont.

Postsynaptically acting drugs Postsynaptically acting drugs

A-Drugs that decrease transmissionA-Drugs that decrease transmission

B-Drugs that increase transmissionB-Drugs that increase transmission

Drugs that affect skeletal muscles; cont.Drugs that affect skeletal muscles; cont.

Drugs that decrease transmissionDrugs that decrease transmission

Non-depolarizingNon-depolarizing

(Competitive)(Competitive)DepolarizingDepolarizing

(noncompetitive)(noncompetitive)

MOAMOA Competing with Ach Competing with Ach at NmRat NmR

Excessive Excessive depolarization→ depolarization→ transmission failure transmission failure &R blockage&R blockage

ExamplesExamples Tubocurarine Tubocurarine

GallamineGallamineSuccinylcholine Succinylcholine

Decamethonium Decamethonium

Type of paralysisType of paralysis

producedproduced

Flaccid Flaccid Spastic Spastic

Drugs that affect skeletal muscles; cont.Drugs that affect skeletal muscles; cont.

Drugs that increase transmissionDrugs that increase transmission

Cholinesterase inhibitorsCholinesterase inhibitorsA- ReversibleA- Reversible

e.g. neostigmine, physiostigminee.g. neostigmine, physiostigmine

B- IrreversibleB- Irreversible

e.g. organophosphorus insecticides e.g. organophosphorus insecticides

* Both will lead to accumulation of Ach at myoneural junction * Both will lead to accumulation of Ach at myoneural junction

NAch 0.05ml

W N

Ach 0.1ml

W+N W+N W+N

0.2mlAch

0.4mlAch

PART 1

A

B

Height = A-B

N

W+N

Ph

ysio

steg

min

e0

.1m

l

W+N

0.1mlAch

0.1mlAch

Cu

rare

0.2

ml

0.1mlAch

PART 2

Curves

0.1mlAch

W+N

CurvesCurves

**

*

Dose

Ht.

On semi-log paper On normal paper

Dose

Ht.