Physio of the NMJ Flashcards
What enzyme causes the creation of acetylcholine?
Choline acetyltransferase (ChAT) combines acetyl coa from within the axon terminal with choline that was from the outside of the cell that came in via choline receptors
What do patients with alzheimers have less of?
Choline acetyltransferase
What are the VAMPS that are housed on the synaptic vesicle?
Synaptobrevin and synaptotaxin
What are the SNAPS that are housed on the axon membrane?
SNAP25 and Syntaxin
What is needed for the creation of the SNARE complex that fuses the synaptic vesicle with the plasma membrane of the axon?
Calcium influx that is caused from the sodium influx of the AP
What is responsible for the inhibition of acetylcholine in the synaptic cleft?
Acetylcholinesterase (AchE) - an enzyme that destroys ACH and breaks it up into acetyl coa and choline that is recycled
What receptors does ACH bind to on the muscle fiber?
Nicotinic acetylcholine receptors (NAchR)
What is the action of NAchRs?
Allow a lot of sodium into the cell and allow some potassium out of the cell
As the depolarization travels down the T-tubule, it reaches receptors… what are those receptors?
Dihydropyradine receptors that are attached to ryanodine receptors on the terminal cisternae
What is the action of the dihydropyradine receptors?
They pull off the ryanodine receptors and allow calcium out of the terminal cisternae so it can bind to troponin and allow sarcomere/muscle contraction
What creates the resting membrane potential?
Sodium/potassium pump (pumps 2 K in and 3 Na out) and leaky K+ channels that allow potassium to leave the cell and follow conc. gradient which results in a more negative cell
What inhibits the choline receptors on the axon?
Hemicholinium
What inhibits ACH from being transported into synaptic vesicles?
Vesamicol
What destroys the SNARE complex and does not allow synaptic vesicle fusion?
Botulinum toxin
What are the agents that affect the nerve AP?
Tetrodoxin and local anesthetics
Tetrodoxin
Inhibits voltage gated sodium channels and blocks axonal conduction “pufferfish poison”
symptoms = weakness, dizziness, paralysis, death
Local anesthetics
Such as lidocaine, inhibit voltage gated sodium channels and inhibit axonal conduction, used for pain control
What are the agents that block vesicular ACH release?
Botulinum toxin and tetanus toxin
Botulinum toxin
Cleaves SNARE complex which prevents ACH release from synaptic vesicle; sound on fruits, veggies, seafood
Symptoms: blurred vision, nausea, vomiting, diarrhea;
Clinically - used to limit face wrinkles and stop migraines
Tetanus toxin
Found in soil; Targets synaptobrevin and then transported retroaxonally to spinal cord where it inhibits spinal interneurons that serve to relax skeletal muscle
Symptoms: muscle spasms, trismus (lockjaw), stiff neck, rigid abdomen, autonomic overactivity - tachycardia, sweats
What are the agents that affect depolarization?
Agonists and Antagonists of NAchR, curare alkaloids, succinylcholine
What do agonists do?
Bind to receptor and open it
What do antagonists do?
Bind to receptor and keep it closed
Curare alkaloids : d-tubocurarine
Competes with ACH to bind to NAchR, blocks opening of receptor and leads to muscle flaccid paralysis
- Used to relax muscle in surgery and overcome by increased ACH
- Keeps gates closed on receptor
Succinylcholine
Depolarizing neuromuscular blocker; binds to NAchR and initially causes depolarization but leads to receptor blockade and paralysis
- Effects reversed with time
- Binds and opens receptor but then blocks it
What are the agents that inhibit AchE?
Acetylcholinesterase inhibitors
Acetylcholinesterase inhibitors
Block enzymatic activity which results in a high concentrations of ACH at the NMJ
What are the clinical uses of AchE inhibitors?
Used to treat dementia in alzheimers/parkinson’s pts, myasthenia gravis, nerve gas, organophosphate pesticide, reversal of neuromuscular blockade during anesthesia
What are the agents that affect muscle contraction?
Dantrolene
Dantrolene
Inhibits ryanodine receptors and prevents calcium release so no muscle contraction
- Clinically used to treat malignant hyperthermia and spasticity
Site where electrical signal from one excitable cell is communicated with another
Synaptic transmission
What are the 2 types of synaptic transmission?
Electrical (heart) and chemical (uses NT)
How many innervations from a presynaptic cell does the muscle fiber receive?
1
What causes muscles to lose tension despite continuing stimuli?
Fatigue
What are the 2 types of fatigue?
Peripheral (requires availability of ATP) and central (Brought on by buildup of byproducts from contraction such as lactic acid and H+)
What are the 3 fiber types?
Slow twitch oxidative, fast twitch glycolytic and fast twitch oxidative
What energy does slow twitch oxidative use?
O2
What energy does fast twitch glycolytic use?
Phosphocreatine and glucose
What does the force of contraction depend on?
Starting length of sarcomere and how rapidly a fiber is stimulated by a nerve
What is tetanus?
Overlap of muscle twitches such that complete relaxation between them is not achieved
Neurons that innervate more fibers will generate a smaller or greater force?
GREATER
What happens to a muscle with glycolytic fibers?
Generates more force but fatigues quickly
