TOPIC-II

NERVE- MUSLCE PHYIOSLOGY

Neuromuscular Junction

Ultrastructure NMJ

Ultra structure of the Acetylcholine receptor.

Miniature end Plate Potential and Generation of action Potential in Muscle

Drug affecting NMJ by

Dr S. Aijaz A. Rizvi

• Neuromuscular junction Transmission of Impulses from

Nerve Endings to Skeletal Muscle Fibers occur through Neuromuscular Junction.

NMJ

In the axon terminal are many mitochondria that supply adenosine triphosphate (ATP), used for synthesis of an excitatory transmitter acetylcholine.

The opened acetylcholine channel has a diameter of about 0.65 nanometer, which is large enough to allow the important positive ions—sodium (Na+),potassium (K+), and calcium (Ca++)—to move easily through the opening. Conversely, negative ions, such as chloride ions, do not pass through because of strong negative charges in the mouth of the channel that repel these negative ions.

End Plate Potential and Action Potential

• Opening of nACh receptor channels produces an end plate potential, which will normally initiate an AP if the local spread of current is sufficient to open voltage sodium channels. •What terminates the

process?

•acetylcholinesterase

40

0

-40

-80

mV

0 15 30 45 60 75

mSec

nAChr

Na channel

• ACh released into the neuromuscular

junction binds to, and opens, nicotinic ACh

receptor channels on the muscle fiber

membranes (Na+, K+, Ca2+).

•

- at the motor endplate -

Drugs That Stimulate the Muscle Fiber by Acetylcholine-Like Action. methacholine, carbachol,and nicotine,have the same effect on the muscle fiber as does acetylcholine. These drugs are not destroyed by cholinesterase or are destroyed so slowly that their action often persists for many minutes to several hours. Drugs That Stimulate the Neuromuscular Junction by Inactivating Acetylcholinesterase. neostigmine, physostigmine, and diisopropyl fluorophosphate, inactivate the acetylcholinesterase in the synapses so that it no longer hydrolyzes acetylcholine. (diisopropyl fluorophosphate, military potential as a powerful “nerve” gas poison) Drugs That Block Transmission at the Neuromuscular Junction. A group of drugs known as curariform drugs can prevent passage of impulses from the nerve ending into the muscle. For instance, D-tubocurarine blocks the action of acetylcholine on the muscle fiber blocking acetylcholine receptors. Muscle relaxant neuromuscular blockers:(Succinylcholine) act by interfering with transmission at the neuromuscular end used during surgical procedures and in intensive care and emergency medicine to cause temporary paralysis. Spasmolytics.(Methocarbamol) "centrally acting" muscle relaxants, are used to alleviate musculoskeletal pain and spasms and to reduce spasticity in a variety of neurological conditions.

Curariform drugs (D-turbocurarine) block nicotinic ACh channels by competing for ACh binding site reduces amplitude of end plate Potential therefore, no AP

Drug Effects on End Plate Potential - Inhibitors

Botulinum toxin • decreases the release of Ach from nerve terminals • insufficient stimulus to initiate an AP

EMG

EMG