1. Dose response curve of Ach & the effect of different drugs on the isolated frog rectus abdominis Lab # 5

2. Objectives  Describe frog rectus abdominis  Discuss neuromuscular transmission  Compare N N R with N M R  Explain drugs act on neuromuscular transmission

3. 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 CNS Voluntary motor nerve Nm R Neuromuscular(myoneural) junction

4. Neuromuscular transmission

5. 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

6. *flash2 Illustration of neuromuscular transmission

7. Comparison between Nn & Nm NnNm smooth muscle smooth muscle skeletal muscle Located in ganglia Located postsynaptically(MEP)

8. Drugs that affect skeletal muscles 1- Centrally acting drugs e.g. Diazepam (skeletal ms. relaxant) 2- Peripherally acting drugs a- Presynaptically (motor nerve) a- Presynaptically (motor nerve) b- Postsynaptically (sk.ms.) b- Postsynaptically (sk.ms.)

9. Drugs that affect skeletal muscles; cont. Presynaptically acting drugs 1- ↓ AP propagation e.g. local anesthetics e.g. local anesthetics 2- ↓ Ach synthesis e.g. hemicholinium, vesamicol e.g. hemicholinium, vesamicol 3- ↓ Ach release e.g. botulinum toxin e.g. botulinum toxin 4- ↓ calcium conc. e.g. Magnesium e.g. Magnesium

10. Drugs that affect skeletal muscles; cont. Postsynaptically acting drugs A-Drugs that decrease transmission A-Drugs that decrease transmission B-Drugs that increase transmission B-Drugs that increase transmission

11. Drugs that affect skeletal muscles; cont. Drugs that decrease transmission Drugs that decrease transmission Non-depolarizing(Competitive)Depolarizing(noncompetitive) MOA Competing with Ach at NmR Excessive depolarization→ transmission failure &R blockage ExamplesTubocurarineGallamineSuccinylcholineDecamethonium Type of paralysis producedFlaccidSpastic

12. Drugs that affect skeletal muscles; cont. Drugs that increase transmission Cholinesterase inhibitors A- Reversible e.g. neostigmine, physiostigmine e.g. neostigmine, physiostigmine B- Irreversible e.g. organophosphorus insecticides e.g. organophosphorus insecticides * Both will lead to accumulation of Ach at myoneural junction

13. N Ach 0.05ml W N Ach 0.1ml W+N 0.2ml Ach 0.4ml Ach PART 1 A B Height = A-B N W+N Physiostegmine 0.1ml W+N 0.1ml Ach 0.1ml Ach Curare 0.2ml 0.1ml Ach PART 2 Curves 0.1ml Ach W+N

14. Curves * * * Dose Ht. On semi-log paper On normal paper Dose Ht.