Flashcards in Membranes and receptors 5 Deck (80)
What ion channels are present in nerve terminals?
Voltage-gated Na+ channels
Voltage-gated K+ channels
Voltage-gated Ca2+ channels
What effect does an action potential arriving at a nerve terminal have?
Depolarisation opens voltage-gated Ca2+ channels. This is therefore a means by which you can regulated neurotransmitter release from the axon terminal.
Why does the small influx of Ca2+ into the nerve terminal have such a big effect?
Because the intracellular [Ca2+] is kept so low, this influx raises the intracellular concentration significantly.
Voltage-gated Ca2+ channels are structurally similar to what other type of voltage-gated channel?
Where are phosphorylation sites found on Ca2+ and Na+ voltage-gated channels?
Cytoplasmic side - therefore can be phosphorylated by intracellular messengers e.g. by PKA in sympathetic activation (e.g. to increase heart rate).
Where are glycosylation sites found on Ca2+ and Na+ voltage-gated channels?
In Na+ and Ca2+ voltage-gated channels, which subunit is the pore-forming subunit and what is the function of the other subunits?
The alpha-subunit forms the pore and the other subunits fine-tune the properties and enable correct regulation of channel activity.
What is the neuromuscular junction?
The synapse between a nerve and a skeletal muscular fibre.
Describe the mechanism of neurotransmitter release into the neuromuscular junction.
1.Ca2+ entry through Ca2+ channels
2. Ca2+ binds to synaptotagmin
3. Vesicle brought close to membrane
4. Snare complex makes fusion pore
5. Transmitter released through this pore
Where are L-type Ca2+ channels found?
Muscles, neurones and lungs
What drug can block L-type Ca2+ channels?
Dihydropyridines e.g. Nifedipine
What is a muscle spindle?
A sensory receptors in the belly of a muscle that primarily detects changes in the length of this muscle and conveys the information via sensory neurones to the CNS. The brain processes this information to determine the position of the body parts.
What type of ion channel is nicotinic acetylcholine receptor channels?
Ligand-gated ion channels (intrinsic ion channels).
Binding of acetyl choline to nicotinic acetyl choline receptor channels causes what to occur?
1. Binding of 2 ACh to receptors opens intrinsic channel
2. Channel is non-specific to ions and lets Na+ and K+ through (and a small amount of Ca2+)
3. Influx of Na+ exceeds efflux of K+, as Na+ is further away from its equilibrium potential
4. Depolarisation of the sarcolemma occurs
5. This will try to reach reversal potential (no net change of Na+ across the membrane)
What is meant by the reversal potential or Nernst potential?
The membrane potential of an ion at which there is no net (overall) flow of that particular ion from one side of the membrane to the other.
How many ACh need to bind to nicotinic acetylcholine receptor channels to open the ion channel?
What happens to ACh in the synaptic cleft
It diffuses across the cleft can bind to acetylcholine receptor channels but is quickly broken down by acetlycholinesterase.
How does ACh causes nicotinic ACh channels to open?
ACh binds to each alpha-subunits (x2) and causes a conformational change in the receptor which causes the pore to open.
What is the end plate potential?
The depolarizations of skeletal muscle fibers caused by neurotransmitters binding to the postsynaptic membrane in the neuromuscular junction.
What happens to the end plate potential when the external Ca2+ is lowered?
End plate potentials decrease in amplitude, as the equilibrium potential of Ca2+ decreases.
Transmitter release from the pre-synaptic membrane is dependent on what?
How does curare/ d-tubocurarine (a poison used to hunt for food in the amazon) cause paralysis?
It is a compeitive antagonist. It blocks transmission between nerve and muscle fibre by competitively blocking nicotinic acetlycholine receptors. It binds to the receptors but does not open the channel.
How can paralysis by d-tubocurarine (d-TC) be overcome?
It does not bind the acetlycholine receptors forever, therefore high concentrations of acetycholine can overcome this block.
How is a muscle AP triggered from the binding of ACh to nicotinic ACh receptor channels?
1. Channels open
2. Na+ influx (greater than K+ efflux) depolarises sarcolemma -> end plate potential
3. Depolarisation activates adjacent Na+ channels due to local spread of charge and causes the muscle AP.
What is the mechanism of action of depolarising blockers like succinylcholine?
They bind to ACh receptors and cause the channels to open and remain open. This continued depolarisation leads to inactivation of the adjacent Na+ channels as they become accomodated.
What are minature end-plate potentials?
They are small depolarisations (1mV) of the sarcolemma caused by the spontaneous release of vesicles (about 1 per second). These depolarisations are too small to trigger an muscle AP.
What is Myasthenia gravis?
An autoimmune disease targeting nACh receptors that causes patients to have profound muscle weakness which increases during exercise.
What is the mechanism of action of myasthenia gravis?
Antibodies directed against nAChR on postsynaptic membrane of skeletal muscle causes loss of function nAChR by complement mediated lysis and receptor degradation. Endplate potentials are reduced in amplitude leading to muscle weakness and fatigue.
What would happen to the minature end plate potenitals of an individuals suffering myasthenia gravis?
They would decrease in amplitue because there are less nAChR available.