Neurological Diseases: Module 2.10 - 2.11 Flashcards
What was the first chemical synapse to be discovered in detail?
Synapse at the neuromuscular junction.
Most studied synaptic connection.
Who won the Nobel Prize for the discovery of mechanisms at the neuromuscular junction?
Sir Bernard Katz
How many synapses occur between the motor neuron and the target tissue?
1 Synapse
Describe all the structural components of the neuromuscular junction.
* End Plate: Specializeed synapses between mtor neurons and skeletal muscle.
- Motor Unit: Group of muscle fibers innervated by the axon from one motor neuron.
- NMJ: Single point of synaptic contact between axon and muscle fiber.
- Post Junctional Folds: Invagination of Postsynaptic membrane. Greatly increase surface areas. Very high density of nicotinic Ach recptors.
- Active Zone: Regions in which vesicles fuse with presynaptic membrane and release ACh.
- Basal Lamina: contains proteins that mediate adhesion, including AChE, which hydrolyzes ACh to choline and acetate.
Where are the N type Pre-synaptic Calcium channels in relation to the postsynaptic receptors?
Aligned exactly opposite.
What causes the sharp local rise of calcium in the presynaptic terminal and not further in the neuron?
Ca ions do not diffuse long sdistances from their site of entry because free Ca is rapidly buffered by Ca binding proteins.
Acetylcholine receptors in the vertebrate neuromuscular junction are concentrated at the ____ of the junction folds.
Acetylcholine receptors in the vertebrate neuromuscular junction are concentrated at the top 1/3 of the junction folds.
How does the activation of Ach channels at the top of the junctional folds result in a action potential further in the muscle?
ACh depolarization allows opening of voltage gated Na channels at the bottom of the junctional folds.
The depolarization is normall large enough to open a sufficient number of Na channels to exceed the threshold for an action potential.
What are the 4 types of Motor Unit Disorders?
- Motor Neuron Diseases (Cell Body)
- Peripheral Neuropathies (Axon and Myelin)
- Disorders of the Neuromuscular Junction
- Myopathies (Primary Mucle Diseases)
What is ALS?
Amyotrophic Lateral Sclerosis
Symptoms:
- Usually starts with painless weakness in a single arm or leg.
- Trouble in Executing fine movements of the hand.
- This focal weakness then spreads over 3 or 4 years to involve all four limbs, as well as the muscles of chewing, speaking, swallowing and breathing. Fatal.
**Cause: **
Most cases involve both the upper and lower motor neurons; however the cause of 90% of the cases is not known.
Treatment:
No effective treatment.
Hereditary? - About 10% of cases are inherited in a dominant manner.
What is CMT Type 1?
Charcot-Marie-Tooth Disease Type 1
Demylinating neuropathy results in smaller, waker muscles. Conduction is peripheral nerves is slow, with histological evidence of demylination followed by remylination.
Progressive - No remissions or exacerbations.
Transfer: Autosomal Dominant
Can affect all peripheral myelinated nerves.
What is CMT Type 2?
Charcot-Marie-Tooth Disease Type 2
Has normal nerve conduction velocity and is considered an axonal neuropath without demyelination. Involves axonal degeneration.
Transfer: Autosomal Dominant
Can affect all peripheral myelinated nerves.
What is Myasthenia Gravis?
Myasthenia means muscle weakness.
Neuromuscular Junction Disease - Best Studied
Symptoms:
* Weakness greatest at the end of the day.
* Myasthenic Fatigue; Musckles that may seem normal at first become waker with continued use.
* Fatigue is exacerbated by physical activity, stress, illness, and heat.
* Can lead to death due to paralysis of respiratory muscles.
Autoummune disorder: Attacks Nicotinic AChRs
What are possible treatments of Myasthenia Gravis?
- Enhancement of Cholinergic Transmission (AChE inhibitors)
- Thymectomy
- Immunosuppression
Explain the full mechanism of Myasthenia Gravis?