Neuromuscular Junction Flashcards
1
Q
What is a Neuromuscular Junction?
A
Is the place where the motor neuron makes a functional contact with the skeletal muscle fiber
- Is a specialized form of a chemical synapse comprised of an alpha motor neuron and the muscle fiber it innervates
- Is the point of communication between the nerve & muscle fiber
2
Q
What are terminal boutons?
A
- Innervate muscle fiber
- Are the site of NMJ
- AP jumps along Nodes of Ranvier ending at terminal bouton
- Myelin sheath surrounding the motor axon ends near the surface of the muscle fiber & the axon divides into a number of short processes that lie embedded in grooves on muscle-fiber surface
- Acetylcholine is stored & released here
3
Q
What is the synaptic cleft?
A
- Folds of the synaptic trough
- ↑post-synaptic SA
- Are the location of maj. of acetylcholine receptors (ligand gated Na+ & K+ Channels)
4
Q
What are Acetylcholine receptors?
A
- 5 subunits
- 2 ACH mols attach to the 2 alpha subunits -> opening channel
- Resting state = closed
5
Q
How does an Action Potential move across the NMJ?
A
- AP arrives at terminal bouton
- Depolarization causes Ca2+ channels to open -> Ca2+ into cell
- This triggers release of Ach from vesicles by exocytosis
a. 4 Ca2+ for 1 Ach vesicle exocytosis- ACh released into synaptic cleft
- ACh binds to nicotinic cholinergic receptors at motor end-plate opening ion channels
- Na+ flows into muscle cell & causes an end plate potential that is sufficient to trigger an AP
a. Depolarization produced by Na+ entering cell after ACh binding = Excitatory Postsynaptic Potentials (EPSP’s) - The flow of Na+ ions across the membrane into the muscle cell generates an action potential which travels to the myofibril & results in muscle contraction
6
Q
What are End Plate Potentials?
A
- Have NO Threshold – single quantum of ACh (released from single vesicle) produces a tiny depolarization of postsynaptic membrane
- ↑quanta of ACh released -> ↑depolarization
- Graded in magnitude – not ‘all or none’ response
- Are capable of summation – have no refractory period
- Strength determined by:
o Amount of neurotransmitter released
o Time the neurotransmitter is in the area
7
Q
What are the types of End Plate Potentials?
A
- Types of post-synaptic potentials:
o EPSP – excitatory postsynaptic potentials
o IPSP – inhibitory postsynaptic potentials
8
Q
What are Excitatory Postsynaptic Potentials?
A
- Neurotransmitter binds to & opens chemically gated channels that allow simultaneous flow of Na+ & K+ in opposite directions
- Na+ influx > K+ efflux = net depolarization
- EPSP helps trigger AP at post synaptic membrane
o If EPSP = threshold strength -> opens voltage-gated Na+ channels along post synaptic membrane
9
Q
What are Inhibitory Postsynaptic Potentials?
A
- Neurotransmitter binds to & opens channels for K+ & Cl-
- Causes hyperpolarization (inside cell becomes negative)
- Reduces postsynaptic neuron’s ability to produce an action potential
- Glycine & GABA
10
Q
How is free ACh recycled?
A
- Free ACh must be inactivated v soon after release in order for activity in postsynaptic cell to be controlled.
- Inactivation of ACh either:
o Acetylcholinesterase hydrolyses it into Acetate & Choline
o Defuses away - Acetylcholinesterase acts only on unbound ACh
- Choline transported back into nerve terminal
- Combines with Acetyl CoA
11
Q
What is the SNARE complex?
A
o Proteins that bridge vesicle membrane and presynaptic membrane in docking
o Synaptobrevin – vesicle membrane protein
o Syntaxin & SNAP-25 : anchored plasma membrane proteins
12
Q
What is the process of exocytosis of synaptic vesicles?
A
- AP arrives at presynaptic terminal button -> depolarization opens voltage-gated Ca2+ channels in plasma membrane
- Ca2+ enters cytoplasm -> attaches to Ca2+ sensor protein – Synaptotagmin, which is anchored to the synaptic vesicle membrane
- Synaptotagmin interacts with SNARE complex:
a. Munc18 guides assembly of trans-SNARE complex assembly
b. Synaptobrevin intertwines with Syntaxin & SNAP-25 to form a rope
c. This pulls the vesicle down towards the membrane - Ca2+ also triggers fusion pore opening via synaptotagmin
- The 2 membranes fuse & SNARE proteins come together within same membrane
a. Now referred to as the cis-SNARE complex - Lipid rearrangement (Membrane fusion) -> fusion pore opens, allowing ACh in vesicle to leak into outside ECF.
- NSF fusion proteins & alpha-SNAP disassemble the SNARE complexes with the help of ATP -> allows another synaptic vesicle to attach
13
Q
How are vesicles recycled?
A
3 pathways are proposed by which the now empty vesicles can be recovered and retured to the releasable pool:
- Vesicles are recycled by a direct reclosing of the fusion pore & reformation of the vesicle, often called ‘kiss & run’.
- Vesicles are recycles by complete fusion (flattening of vesicles onto membrane surface) followed by:
a. Clathrin-mediated endocytosis
b. Removal of clathrin coat
c. Return of vesicle to releasable pool - Vesicles are recycled by complete fusion & recycling like in 2. – but endocytosed vesicles fuse first with endosome & mature vesicles subsequently formed by budding from endosome
a. After/during this recycling process, vesicle must be refilled with neurotransmitters
14
Q
What are 3 chemical agents that affect the NMJ?
A
- Botulinum toxin
- Curare
- Black Widow Spider Venom
15
Q
What effect does Botulinum toxin have on the NMJ?
A
- Neurotoxin protein produced by a bacterium found in improperly canned food
- Blocks release of neurotransmitters
- Is a protease that destroys speciiffc proteins of SNARE complex -> inhibiting exocytosis of neurotransmitters
- Targerts excitatory synapses that release ACh & digests Snyaptobrevin
- Infection could result in Botulism – potentially fatal
o Causes characteristic flaccid paralysis
