Neuro-Muscular Junction 3Dr. Sumera Gul

Associate Professor

Department of Physiology

LEARNING OBJECTIVES

At the end of the session, the students should be able to:

• Discuss the drugs blocking the Neuro-muscular junction.

• Discuss the Drugs That Stimulate the Neuromuscular Junction

• Discuss the drugs that Stimulate the Muscle Fiber by Acetylcholine-

Like Action.

• Discuss the features of Myesthenia Gravis and related

pathophysiology.

Review of previous lecture

Figure 9.9

Na+

Na+

Open Na+

Channel

Closed Na+

Channel

Closed K+

Channel

Open K+

Channel

Action potential+++++

++++++

+

Axon terminal

Synapticcleft

ACh

ACh

Sarcoplasm of muscle fiber

K+

2 Generation and propagation of

the action potential (AP)

3 Repolarization

1 Local depolarization:

generation of the end

plate potential on the

sarcolemma

K+

K+Na+

K+Na+

Ca2+ is pumped backTakes ATP

Muscle Fatigue

Drugs affecting Neuromuscular Junction

Drugs that Stimulate Muscle Fiber by Ach like action

• Carbachol

• Nicotine

• Methacholine

Drugs that inactivate Acetylcholinesterase

• Neostigmine

• Physostigmine

• Di-isopropyl fluorophosphate

Drugs that Block neurotransmission at NMJ

• Curariform drugs

• D-Tubocurarine

Examples of Chemical Agents and Diseases that Affect the Neuromuscular Junction

Mechanism Chemical Agent or Disease

Alters Release of Acetylcholine

* Cases explosive release of acetylcholine * Black widow spider venom

* Blocks release of acetylcholine * Clostridium botulinum toxin

Block acetylcholine Receptor

* Bind reversibly * Curare

* Auto antibodies inactivate acetylcholine * Myasthenia gravis

receptors

Prevents inactivation of acetylcholine

* Irreversibly inhibits acetylcholinesterase * Organophosphates

* Temporary inhibits acetylcholinesterase * Neostigmine

A: curare, a drug that blocks the gating action of acetylcholine on the acetylcholine channels by competing forthe acetylcholine receptor sites.

C: botulinum toxin, a bacterial poison that decreases the quantityof acetylcholine release by the nerve terminals.

Myasthenia Gravis

Myasthenia Gravis

• Occurance: 1 in every 20,000 persons,

• Symptoms: Muscle weakness

• Pathophysiology: Auto-immune disorder . Antibodies that attack the acetylcholine receptors

• Antibodies block or destroy their own acetylcholine receptors at the postsynaptic neuromuscular junction.

• This leads to inability of the neuromuscular junctions to transmit enough signals from the nerve fibers to the muscle fibers.

• If the disease is intense enough, the patient may die of respiratory

failure as a result of severe weakness of the respiratory muscles.

• Neostigmine or some other anticholinesterase drug, which allows

larger than normal amounts of acetylcholine to accumulate in the

synaptic space.

Questions?