SKELETAL MUSCLE: NEUROMUSCULAR JUNCTION Flashcards
Describe the 2 components and 3 distinct regions of the neuromuscular anatomy
2 components: motor neuron and muscle fibre
3 distinct regions: presynaptic region, synaptic cleft, and post-synaptic region
Define: motor unit
A motor unit is one motor neuron and all the fibres it innervates. one motor neuron, axon, presynaptic terminals (bouton), muscle fibres.
Define: end plate
where presynaptic terminal of nerve cell meets postsynaptic region of muscle cell
Define: innervation ratio
When do you need a larger innervation ratio?
number of muscle fibres supplied by one motor neuron
For gross movement or movement where you need high force production, innervation ratio is larger.
Describe the 7 steps involved in synaptic release
- Neurotransmitter molecules are synthesized and packaged in vessels
- An action potential travels down axon and arrives at the presynaptic terminal
- Voltage-gated Ca2+ channels open due to depolarization of AP.. Ca2+ enters
- A rise in Ca2+ triggers fusion of synaptic vesicles with the presynaptic membrane
- Transmitter molecules diffuse across the synaptic cleft and bind to specific receptors on the postsynaptic cell
- Bound receptors activate the postsynaptic cell
- A neurotransmitter breaks down, is taken up by the presynaptic terminal or other cells, or diffuses away from the synapse
What is the function of the presynaptic termini? What does it require?
Presynaptic termini function: synthesis, storage and release of ACh (synthesized from choline and acetyl-CoA; stored in synaptic vesicles)
Requires choline acetyltransferase (ChAT)
What is a quantum?
Describes the # of ACh molecules a vesicle stores (6000-10 000)
Describe vesicular movement in the presynaptic neuron
- Docking stage: Synaptobrevin (v-SNARE protein) and syntaxin/SNAP-25 (two t-SNARE proteins) form a zippered complex (trans-SNARE complex) to bring the vesicle and its target into proximity,
- Priming stage 1: Complexin (grappling protein) primes the trans-SNARE complex for interaction with synaptotagmin
- Kiss stage or fusion-pore opening stage: Ca2+ enters and binds to synaptotagmin (now collectively called Ca2+-bound synaptotagmin), displacing complexin and binding to the SNARE complex. This results in membrane fusion and formation of the fusion pore
- Run stage: [Ca2+] falls rapidly as mitochondria uptakes it and subsequently synaptotagmin dissociates from the SNARE complex. The SNARE complex dissasembles and the vesicle undergoes endocytosis (in this context, closes so that it is empty and now can be re-used). Synaptobrevin is recycled for re-use
What is the function of the v-SNARE proteins? List two v-SNARE proteins.
v-SNARES catch t-SNARES to pull vesicles close to the membrane
Two v-SNARE proteins: Synaptobrevin and synaptotagmin
Both form a zipper with t-snares
What is the function of nicotonic acetylcholine receptors? describe its structure as well
Nicotonic acetylcholine receptors: a postsynaptic transmembrane protein
. specifically, a neurotransmitter-gated ion channel that has been fine-tuned through evolution to transduce a chemical signal into an electrical signal with maximum efficiency and speed
- Heteromeric pentamer with 2 alpha, 1 beta, 1 delta and 1 epsilon subunit
- 2 molecules of ACh bind causing a conformational change that ”opens” the channel allowing sodium and potassium ions to move down their electrochemical gradient
- This produces an end plate potential (EPP)
What are mEPPS?
Describe the following toxin and its effect on a human and its effect at the NMJ: tetrodotoxin
Describe the following toxin and its effect on a human and its effect at the NMJ: saxitoxin
Describe the following toxin and its effect on a human and its effect at the NMJ: dendrotoxin (DTX)
Describe the following toxin and its effect on a human and its effect at the NMJ: tetanus toxin (TNTX)
Describe the following toxin and its effect on a human and its effect at the NMJ: Botuluism toxin (BTX)
