Shaweta Khosa

Neuromuscular Junction-Neuromuscular Junction A neuromuscular junction exists between a motor neuron and a skeletal muscle.

- Synapse A junction between two neurons

INNERVATION OF SKELETAL MUSCLE FIBERS

•Large, myelinated nerve fibers•Originate from large motor neurons in the anterior horns of the spinal cord•Each nerve fiber, branches and stimulates from three to several hundred skeletal muscle fibers•The action potential initiated in the muscle fiber by the nerve signal travels in both directions toward the muscle fiber ends

MOTOR END PLATE

•The nerve fiber forms a complex of branching nerve terminals that invaginate into the surface of the muscle fiber but lie outside the muscle fiber plasma membrane• Entire structure - motor endplate. •Covered by one or more Schwann cells that insulate

it from the surrounding fluids.

AXON TERMINAL

•SYNAPTIC VESICLES • Size 40 nanometers • Formed by the Golgi apparatus in the cell body of the

motor neuron in the spinal cord. • Transported by axoplasm to the neuromuscular junction

at the tips of the peripheral nerve fibers.• About 300,000 of these small vesicles collect in the nerve

terminals of a single skeletal muscle end plate.

•MITOCHONDRIA •Numerous•Supply ATP •Energy source for synthesis of excitatory

neurotransmitter, acetylcholine

•DENSE BARS •Present on the inside surface of neural membrane

•VOLTAGE GATED CALCIUM CHANNELS

• Protein particles that penetrate the neural membrane on each side of dense bar•When an action potential spreads over the terminal, these channels open and calcium ions diffuse to the interior of the nerve terminal.•The calcium ions, exert an attractive influence on the acetylcholine vesicles, drawing them to the neural membrane adjacent to the dense bars.

•The vesicles then fuse with the neural membrane and empty their acetylcholine into the synaptic space by the process of exocytosis•Calcium acts as an effective stimulus for causing acetylcholine release from the vesicles•Acetylcholine is then emptied through the neural membrane adjacent to the dense bars and binds with acetylcholine receptors in the muscle fiber membrane

MUSCLE FIBER MEMBRANE

•SYNAPTIC TROUGH •The muscle fiber membrane where it is

invaginated by a nerve terminal and a depression is formed

•SYNAPTIC CLEFT •The space between the nerve terminal and the

fiber membrane is called the synaptic space or synaptic cleft

•SUBNEURAL CLEFT •Numerous smaller folds of the muscle membrane at

the bottom of the gutter• Greatly increase the surface area.

•ACETYLCHOLINE RECEPTORS • Acetylcholine-gated ion channels• Located almost entirely near the mouths of the sub

neural clefts lying immediately below the dense bar areas

ACETYLCHOLINE RECEPTORS• Acetylcholine-gated ion channels•Molecular weight -275,000•SUBUNITS •Two alpha, one each of beta, delta, and gamma •Penetrate all the way through the membrane• Lie side by side in a circle- form a tubular channel •Two acetylcholine molecules attach to the two alpha

subunits, opens the channel

•RESTING STATE •2 Ach molecules not attached to the alpha subunit •Channel remains constricted

•OPENED Ach CHANNEL

•2 Ach molecules attached to the alpha subunit of receptor •Diameter- 0.65 nanometer•Allows important positive ions—SODIUM,

potassium, and calcium to move easily through the opening. •Disallows negative ions, such as chloride to pass

through because of strong negative charges in the mouth of the channel that repel these negative ions.

•SODIUM IONS

•Far more sodium ions flow through the acetylcholine channels to the inside than any other ions •The very negative potential on the inside of the

muscle membrane, –80 to –90 mili volts, pulls the positively charged sodium ions to the inside of the fiber•Simultaneously prevents efflux of the positively

charged potassium ions when they attempt to pass outward

•END PLATE POTENTIAL

•Opening the acetylcholine-gated channels allows large numbers of sodium ions to pour to the inside of the fiber• Sodium ions carry with them large numbers of

positive charges• Creates a local positive potential change inside the

muscle fiber membrane, called the end plate potential.•End plate potential initiates an action potential that

spreads along the muscle membrane• Causes muscle contraction

Events of Neuromuscular Junction1. Propagation of an action potential to a terminal

button of motor neuron.2. Opening of voltage-gated Ca2+ channels.3. Entry of Calcium into the terminal button.4. Release of acetylcholine (by exocytosis).5. Diffusion of Ach across the space.6. Binding of Ach to a receptor on motor end plate.

Examples of Chemical Agents and Diseases that Affect the Neuromuscular Junction

Mechanism Chemical Agent or DiseaseAlters 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

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