Synapses, neuromuscular junctions Flashcards
What is a neuromuscular junction?
Synpase between motor neurone and skeletal muscle fibre
Which ion channels are located in the neurone terminal?
Votage-gated sodium ion channels
Voltage-gated potassium ion channels
Voltage-gated calcium ion channels
What causes the voltage-gated calcium ion channels in the neurone terminal to open?
Incoming action potential causes neurone terminal to be depolarised
How do calcium ions move through the open voltage-gated calcium ion channels in the neurone terminal?
Move into the neurone terminal
down their concentration gradient
What do the influxed calcium ions in the neurone terminal do?
Bind to synaptotagmin
What does calcium-bound synaptotagmin in the neurone terminal do?
Brings vesicles containing neurotransmitter closer to the pre-synaptic membrane
What neurotransmitter do the vesicles in a neuromuscular junction contain?
Acetylcholine
What do the vesicles containing acetylcholine do when they’re near the pre-synaptic membrane?
Snare complex fuses the vesicle membrane and the pre-synaptic membrane together
acetylchole is released into synaptic cleft
What does acetylcholine in the synaptic cleft do?
Diffuses across synaptic cleft
binds to nicotinic acetylcholine receptors on the skeletal muscle membrane, 2 per receptor
causing it to open
What passes through open nicotinic acetylcholine receptors? What passes through most?
Sodium ions - more of these pass through
Potassium ions
Why do sodium ions largely pass through open nicotinic acetylcholine receptors compared to potassium ions?
Because there is greater driving force for sodium ions to enter the skeletal muscle fibre
since membrane potential is further away from ENa
What happens to the membrane potential of the skeletal muscle fibre due to influx of sodium ions?
Membrane potential depolarises
nearby voltage-sodium ion channels open
action potential is generated
What happens to acetylcholine bound to nicotinic acetylcholine receptors? What is the importance of this?
Broken down by acetylcholinesterase
Terminates the signal from motor neurone to skeletal muscle fibre
so don’t remain contracted
How does increasing the number of action potentials along the axon affect the neurone terminal?
Increased influx of calcium ions
more vesicles fuse with pre-synaptic membrane
more acetylcholine released
What is the structure of a voltage-gated calcium ion channel?
Single polypeptide chain, called alpha subunit
Four parts
Each part is made up of six transmembrane domains
What is the function of the fourth transmembrane domain in a voltage-gated calcium ion channel?
Voltage sensor
What is the significance of the fifth and sixth transmembrane domains in a voltage-gated calcium ion channel?
Between them is pore region
What is the signifiance of the third and fourth parts in a voltage-gated calcium ion channel?
Between them is inactivation particle
Are voltage-gated sodium ion channels or calcium ion channels faster at activating and inactivating?
Voltage-gated sodium ion channels
What causes the inactivation of voltage-gated calcium ion channels?
Calcium ions passing through them
giving increased concentration of intracellular calcium
What are the types of blockers of nicotinic acetylcholine receptors?
Competitive blocker
Depolarising blocker
What is an example of a competitive blocker of nicotinic acetylcholine receptors?
Curare
How do competitive blockers of nicotinic acetylcholine receptors work?
Compete with acetylcholine for ligand-binding site on the nicotinic acetylcholine receptors
block the ligand-binding site
so acetylcholine can’t bind and nicotinic acetylcholine receptors can’t open
How are the effects of competitive blockers of nicotinic acetylcholine receptors overcome?
By increased concentration of acetylcholine
What is an example of a depolarising blocker of nicotinic acetylcholine receptors?
Succinylcholine
How do depolarising blockers of nicotinic acetylcholine receptors work?
Bind to nicotinic acetylcholine receptors and cause them to open
not broken down well by acetylcholinesterase
depolarisation is maintained
voltage-gated sodium ion channels inactivate and do not reactivate due to lack of hyperpolarisation
How do blockers of nicotinic acetylcholine receptors affect muscle contraction?
Muscles don’t contract, are paralysed
What is the pathophysiology of myasthenia gravis?
Autoantibodies against nicotinic acetylcholine receptors
are destroyed
skeletal muscle fibre membrane doesn’t reach threshold
action potential not generated
muscle doesn’t contract
What are the symptoms of myasthenia gravis?
Muscle weakness
Muscle fatigue
What exacerbates the symptoms of myasthenia gravis?
Exercise
What do synapses occur between?
Neurone to neurone
Neurone to muscle fibre
Neurone to gland cell
Sensory cell to neurone
What are the types of synapses?
Fast
Slow
What is a fast synapse?
Neurotransmitter binds to receptor on post-synaptic membrane
which is a ligand-gated ion channel
causing it to open
and allowing ions to pass through
What are the types of fast synapses?
Excitatory
Inhibitory
What are excitatory fast synapses?
The ligated-gated ion channel that opens is for sodium ions or calcium ions, whose influx gives membrane depolarisation
What is the name of the depolarisation caused by excitatory fast synapses?
Excitatory post-synaptic potentials
What are inhibitory fast synapses?
The ligand-gated ion channel that opens is for potassium or chloride ions
whose movement across the post-synaptic membrane gives hyperpolarisation
What is the name of the hyperpolarisation caused by inhibitory fast synapses?
Inhibitory post-synaptic potential
Are excitatory/inhibitory post-synaptic potentials the same as action potentials?
No
How are excitatory/inhibitory post-synaptic potentials different to action potentials?
They are graded, meaning their strength varies
They last for longer than an action potential
How are excitatory/inhibitory post-synaptic potentials graded?
Based on amount of neurotransmitter binding to receptors on post-synaptic membrane
based on number of vesicles fusing with pre-synaptic membrane
based on calcium ion influx
based on frequency of incoming action potentials into pre-synaptic neurone terminal
What are slow synapses?
Neurotransmitter binds to receptors on post-synaptic membrane
signal transduction occurs to open ion channel, which is a separate protein
What are the types of mechanisms by which slow synapses work?
Neurotransmitter binds to GPCR
activated G-protein itself binds to ion channel and opens it up
Neurotransmitter binds to GPCR
signalling cascade
effector protein binds to ion channel and opens it up
Which mechanism of slow synapses is faster? Why?
Where the activated G-protein itself binds to ion channel and opens it up
because it’s more localised
