L9 Neuromuscular Junction

Question 1

Neuromuscular junction

Answer 1

Motor neuron innervating skeletal muscle cells

Question 2

Synaptic vesicles

Answer 2

Contain acetylcholine

Question 3

Active zone

Answer 3

Storage and release sites for vesicles

Question 4

Motor endplate

Answer 4

Sarcolemma opposite to synaptic terminals

Has receptors for ACh

Question 5

ACh receptors

Answer 5

Mixed-cation channel (simultaneous Na into cell and K out of cell)

Highest concentration in junctions (synaptic) folds

Question 6

End plate potential (EPP)

Answer 6

Depolarizing graded potential that results from the opening of ACh receptors

EPP reaches threshold and initiates action potentials

It’s nickname for graded potential

Question 7

NMJ : chemical synapse

Answer 7

Action potential from motor neuron results in release of ACh

Opening of ACh receptors results in an EPP

The EPP depolarizes the motor endplate and initiates actions potential in muscle sarcolemma

Na and K moving though membrane but net effect is always depolarization (graded potential, varies with size of stimulus, decremental propagation, bidirectional)

Question 8

Motor end plate

Answer 8

Region of sarcolemma of skeletal muscle with folds that are enriched with ACh receptors

Question 9

Outside of motor end plate there is

Answer 9

Voltage gated Na and k channels that can make action potentials that travel throughout sarcolemma

Question 10

Motor end plate v sarcolemma

Answer 10

Motor end plate: directly across from synaptic terminal, ion channels chemically gated (bind ACh), capable of EPP not action potentials

Sarcolemma: plasma membrane of muscle fiber, electrically similar to axons plasma membranes (neurons), ion channels voltage gated, propagate action potentials

Question 11

Release, removal, and recycling ACh

Answer 11

ACh binding to receptor very brief

Acetylcholinesterase rapidly degrades ACh into choline and acetate (present in post synaptic folds of synaptic cleft)

Choline returned to presynaptic knob (recycled) reformed with acetyl-coA and in ACh

Question 12

Factors affecting magnitude of EPP

Answer 12

Voltage gated calcium channel function

Amount ACh release

Rate of ACh breakdown

ACh receptors agonists and antagonists

Question 13

Possible actions of pathophysiological conditions or pharmacological agents

Answer 13

Altering synthesis, axonal transport, storage, or release of neurotransmitter

Influencing neurotransmitter reuptake or destruction

Modifying or blocking neurotransmitter interaction with postsynaptic receptor (antagonist)

Replacing a deficient neurotransmitter or amplifying it’s effect with a substitute (agonist)

Question 14

Non polarizing blockers

Answer 14

Competitively bind ACh receptor

Ion channels do not open (blockade)

Insufficient or no EPP

flaccid paralysis

Ex: curare

Blocks muscle but doesn’t depolarize

Question 15

Depolarizing blockers

Answer 15

Prolonged activation of ACh receptor

Continuous depolarization of end plate for 2-3min

Voltage gated Na channels In sarcolemma become inactivated

Contraction follow by flaccid paralysis

Ex: succinylcholine

Permits depolarizing but consequence of prolonged depolarizing still end up blocking muscle function

Question 16

Curare

Answer 16

Poisonous plant extract

Competitively and reversibly inhibit the nicotinic ACh receptor found at NMJ

causes weakness of skeletal muscle

Sufficient does can cause death by asphyxiation due to paralysis of diaphragm

Non depolarizing muscle blocker

Question 17

Anticholinesterases

Acetylcholinesterase inhibitors

Answer 17

Anticholinesterase inhibits acetylcholinesterase allowing ACh to accumulate in synaptic cleft

Low doses - lacrimation, salvation, bradycardia, sweating, vomiting, diarrhea

High doses- fibrillations, muscle twitch, and depolarizing muscular paralysis

Depolarizing blocker (excessive depolarization / paralysis due to inactive Na channels)

Question 18

Examples of anticholinesterases

Answer 18

Organophosphate pesticides and nerve gases

Neostigmine and pyridostigmine - therapeutic drugs

Anectine (succinylcholine) commonly used as a short acting depolarizing muscle relaxant to facilitate tracheal intonations

Question 19

Black widow spider toxin

Answer 19

Contain neurotoxin: latrotoxin which form pores in the lipid membranes and induce Ca flow

Enhances neurotransmitter release (prolonged depolarization)

Symptoms: muscle spasms, intense cramping pain and generalized nervous system excitation

Very high dose - May lead to depolarizing paralysis and death

Depolarizing blocker

Question 20

Lambert-Eaton syndrome

Answer 20

Most often seen in cancer patients

Patients exhibit proximal muscle weakness and autonomic dysfunction

Caused by autoimmune attack on voltage gated Ca channels
Fewer vesicles released in response to
presynaptic action potential and EPP is reduced

Question 21

Lambert Eaton syndrome treatment

Answer 21

3,4-diaminopyridine blocks efflux of K ions prolonging the duration of depolarization

Keeps pathologically affect Ca channels open longer, increasing Ca influx

Question 22

Change in extracellular magnesium

Answer 22

Mg is an essential mineral that regulates neurotransmitter release by blocking some Ca channels

Question 23

Hypomagnesemia

Answer 23

Not enough Mg competing at Ca channels , increasing neurotransmitter exocytosis

Enhanced NMJ transmission (muscle spasms)

Causes: insufficient Mg in diet or impaired uptake

Question 24

Hypermagnesemia

Answer 24

Too much Mg blocks Ca influx , decreasing NT exocytosis

Impaired NMJ transmission

Causes: excessive ingestion of Mg containing drugs (antacids, laxatives)

Question 25

Clostridium botulinum - botulism

Answer 25

Anaerobic organism from soil

Sometimes found in improperly canned food

Blocks fusion of synaptic vesicles with presynaptic membrane by degradation of SNARES proteins

Targets NMJ and cholinergic nerve endings in ANS

Causes flaccid paralysis and death via respiratory paralysis

Used clinically to treat many conditions

Question 26

Myasthenia gravis

Answer 26

Caused by autoimmune antibodies against ACh receptors = diminishes func and numbers

EPP decrease despite normal release of ACh

Symptoms : muscular weakness, blurred vision

Motor improvement with anticholinesterases (pyridostigmine)

Question 27

Why does pyridostigmine provide improvement in myasthenia gravis?

Answer 27

It’s an anticholinesterase/ acetylcholinesterase inhibitor so it enhances ACh level at NMJ

Enhances ACh receptor interaction this improving EPP