Lecture 11. Signaling Via Ligand Gated Ion Channels Flashcards
What is the function of dendrites ?
Collect electrical signals
What synapses onto dendrites ?
Presynaptic terminals
What is the function of cell soma ?
Calculate the overall charge in the soma and will decide whether to trigger an action potential
What do dendrites have ?
Ligand gated ion channels
What is GABA ?
A neurotransmitter
What happens when GABA binds ?
When it binds it opens a chloride channel and makes the interior of the cell more negative, making the cell hyperpolarised and more difficult to fire an action potential
What is the axon hillock ?
The point of exit of the axon from the cell soma
What are the two types of neurotransmitter receptor ?
- Ionotropic
2. Metabotronic
What does an ionotropic receptor have ?
A direct gating of ion channels by the binding of the neurotransmitter
What is an example of an ionotropic receptor ?
Ligand gated ion channels
What happens once a neurotransmitter binds to the ionotropic receptor ?
The gate is lifted and causes protein conformational changes that allows ions into the pore to change the ionic concentration
What do metabotronic receptors have ?
An indirect gating of ion flux altered intracellular metabolic signaling changes
What can ions not flow through ?
The channel, instead the neurotransmitter binds to the receptor
What event occurs when the metabotronic receptor is coupled to a G-protein ?
Signaling event
What happens when the metabotropic receptor is coupled to a G-protein ?
Changes its phosphorylated state and activates effector enzymes like adenyl cyclase
What happens as a result of activating effector enzymes ?
Secondary messengers like cyclic AMP are produced
What can secondary messengers like cyclic AMP do ?
Activates enzymes like protein kinase A
What does protein kinase A do ?
Phosphorylates other proteins in the cell
What does phosphorylation result in ?
Changes the conformation of the ion channel and allows ions to flow
What is the main characteristic of the metabotropic receptor ?
It does not contain an ion channel, it is coupled to the signaling pathway like G-proteins which can induce cellular changes
What are some different types of metabotropic receptors ?
- G-protein receptors
2. Tyrosine kinase receptors
What are acetylcholines two types of receptors ?
- Nicotinic receptors
2. Muscarinic receptors
What type of receptor is nicotinic receptor ?
Ionotropic
What is the nicotinic receptor activated by ?
Nicotine
What is the muscarinic receptor activated by ?
Muscarine
What type of receptor is the muscarinic receptor ?
Metabotropic
What are the roles of muscarinic and nicotinic receptors ?
Cognitive function and cardia and skeletal muscle
What happens when acetylcholine binds to a nicotininic receptor ?
Inflow of sodium leading to depolarisation, voltage gated sodium channels open and allow an influx of sodium which depolarises the muscle cell leading to an end plate potential
What is the structure of the nicotinic receptor ?
Pentamer made up of 5 subunits
What is the structure of the pentameric structure of nicotinic receptor ?
There are two sites for binding acetylcholine
What happens once acetylcholine binds ?
When they binds, they bring about a distortion of the channel such that sodium ions can now flow through the channel
What faces the pore in all pentamer subunits ?
M2 in the alpha helix
What do alpha helical structures have ?
Hydrophobic side chains which project out into the pore of the channel
What happens when acetylcholine binds ?
It twists the protein structure slightly and removes the side chains which allows sodium ions to flow through
What is alpha bungarotoxin ?
A venomous toxin produced by a snake called the bandit crate that irreversibly binds to nicotinic receptors on muscle cells, causing paralysis, death and asphyxiation
What is a myasthenia gravis ?
An autoimmune disorder that develops antibodies against the nicotinic receptors. The receptors are removed by immune cells and muscle weakness and facial paralysis develope
How does acetylcholine slow down the heart rate ?
It is not binding nicotinic receptors but in fact muscarinic receptors
What happens when acetylcholine binds to muscarinic receptors ?
There is no ion flow through this receptor, binding engages the inhibitory G protein
What happens when the inhibitory G protein is activated ?
It is activated inwards rectifying potassium channel that allows potassium to move out of the cell leaving the inside hyperpolarised. This makes it harder to achieve an action potential, so the number of action potentials decreases causing the heart rate to slow
How can the heartbeat be sped up ?
The accelerator nerve using noradrenaline and the beta adrenal receptor
What dictates whether actions are inhibitory or excitatory ?
The receptor the neurotransmitter binds to
How many subunits does glutamate have ?
4 and the transmembrane part does not span the membrane
What is the major excitatory receptor in the brain ?
Glutamate
What is the most common inhibitory in the brain ?
GABA
What does GABA do ?
Regulated the levels of activity in the brain
What are some examples of glutamate metabotropic receptors ?
AMPA, KAINATE, NMDA
What are some examples of glutamate metabotropic receptors ?
mGlurs (mGlur1-mGlur8
What do mGlurs do ?
Affect signalling events
What are AMPA and KAINATE important for ?
Initiating glutamate signaling
What does NMDA do ?
Allows sodium ion influx and calcium entry to the cell
What does NMDA have ?
A magnesium block which prevents the channel opening for sodium can calcium, therefore does not open easily
What is the structure of GABA ?
pentameric structure with the M2 helices forming a channel
What is the GABA channel permeable to ?
Chloride ion and sodium ions
How do chloride ions effect the cell ?
Make the cell more negative - hyperpolarise
What is the GABA ?
an inhibitory neurotransmitter
What is an example of GABA recepotrs ?
- Anaethisia
2. Sedatives
