LG 1.4 - Physiology of Neuromusular Junction Flashcards
What are motoneurons? What are motor units?
- Motoneurons: nerves that innervate muscle fibers.
- Motor units: comprises a single motoneuron and the muscle fibers it innervates.
(2) Excitation-contraction coupling of muscles requires energy from axons to go from Electrical, to Chemical, to Mechanical. Explain each of these individually, aka how does the energy go from electrical -> chemical -> mechanical.
- Electrical: An action potential depolarizes the presynaptic terminal.
- Chemical: Presynaptic terminal releases a neurotransmitter that will create a change in postsynaptic membrane.
- Mechanical: These ultimately result in development of tension in the muscle fiber.
(4) Where is ACh synthesized and where is it placed prior to release into synaptic cleft?
- Synthesized in cytosol of terminal.
- Transported into vesicles.
(4) Roughly how many ACh molecules per vesicle?
- 10,000
(4) What happens to choline after ACh is broken down?
- Choline is reabsorbed by presynaptic terminal to be recycled into more ACh.
(4) Regarding the small vesicles, where are these synthesized and where do they then get transported?
- Golgi apparatus in cell body.
- Transported down to the synapse.
(4) Due to the finite number of vesicles that accumulate at the terminal, what is the process of these becoming regenerated? (from what are they regenerated and how).
- Presynaptic membrane regenerates these vesicles.
- Clathrin proteins contract causing membrane to break away and form new vesicles.
(6) What is the role of Ca2+ in synaptic transmission?
- Ca2+ is involved in the mobilizing and docking of synaptic vesicles.
(7) What is the difference between Endplate Potential and Action Potential?
- Endplate potential: local depolarization of the specialized motor end plate.
- 1 synaptic vesicle creates a miniature endplate potential.
- These endplate potentials add up to reach threshold for an action potential to develop in postsynaptic terminal.
(7) Name the 5 ways that you can disrupt the NMJ?
- Mimicking ACh
- Blocking choline uptake
- Stopping ACh release
- Inactivating ACh esterase
- Blocking the ACh receptor.
(7) Name 3 drugs that mimick ACh and why they can effectively act as ACh?
- Methacholine, carbachol, nicotine.
- Drugs are not destroyed by acetylcholinesterase so they persist in synaptic cleft for many minutes to several hours.
(7) Name a drug which blocks choline uptake, and what would this result in?
- Hemicholinium.
- Blocks choline reuptake into presynaptic terminals -> depleting choline stores from motoneuron terminal and decreasing the synthesis of ACh.
(7) What is the main method of blocking ACh release? What bacterial toxin is used to do this, how? How does black widow venom block ACh release?
- Stop depolarization of presynaptic terminal. Block arrival of action potential.
- Botulinum toxin: prevents docking of the synaptic vesicles.
- Black widow venom: depletes terminal of ACh by binding the synaptic vesicle too good.
(7) What 3 drugs can be used to inactivate acetylcholinesterase? How long do each last?
- Neostigmine, physostigmine, diisopropyl fluorophospate.
- Neostigmine and physostigmine work for hours, diisopropyl fluorophosphate (a nerve gas poison) can last for weeks!
(7) What drugs are used to block the ACh receptor, how do they do this?
- Curariform drugs: bind nicotinic ACh receptor on postsynaptic membrane.
- Succinylcholine is used as muscle relaxant and does this.
(7) What is Myasthenia Gravis, what is the pathology, how is it treated?
- Autoimmune disease in which antibodies are developed that block or destroy their own ACh receptors.
- Endplate potentials are not strong enough to open the voltage-gated Na+ channels so that the muscle fiber does not depolarize. Paralysis of respiratory muscles would be fatal.
- Treat with neostigmine, an acetylcholinesterase inhibitor.
- Read clinical vignette on pg. 28 of Costanzo.
