week 2 - ligand gated ion channels Flashcards
What is the definition of an ion channel?
a channel which is a transmembrane protein that transports molecyules from one side of the membrane to the other. They are specific and can be gated (use carriers).
What are the 3 functions of ion channels?
- Transport ions across the membrane
- Regulate membrane potentials
- Ca influx into the cytoplasm.
Ion channels are classified based on what 2 factors?
- Gating mechanism - if voltage or ligand gated?
- Ion selectivity of the pore - defined by physcial size of ‘filter’ and amino acids lining the pore.
how do TRP channels (Trasnient receptor potential) differ from voltage gated ion channels?
They share common structural features but TRP channels can sense chemicals and stimuli.
What type of receptor is the nicotinic acetylcholine receptor?
a Cys-loop type receptor
- has pentameric assembly - 5 subunits
- M2 lines the pore and makes it selective for specific ions.
- it is involved in reward pathways and nicotine addiction.
What does a mutation in nAChR causes?
causes ADNFLE = autosomal dominant nocturnal frontal lobe epilepsy.
enhanced receptor function –> increased nicotinic mediated transmitter release = ADNFLE seizures.
What type of assesmbly does a glutamate receptor have?
Has tetrameric assembly and has an inverted pore.
The ligand binding site ‘closes’ when occupied.
Where is the GluA2 Q/R site located?
it is located in the M2 of the subunit, inside the channel pore.
What is the role of NMDA?
What happens if there is excess NMDA stimulation in stroke?
NMDA is for controlling synaptic plasticity and mediated learning and memory functions.
Excess stimulation of NMDA in stroke leads to neuron death.
What happens if there is:
downregulation of GluA2 Q/R editing in the motor neurons of ALS patients?
increase in Ca2+ permeable AMPA receptors causes damage due to glutamate excitotoxicity
In glioblastoma, decreased ADAR2 (RNA editing enzyme) activity is correlated with increased malignancy.
how are calcium levels affected?
How can glioblastoma potentially be treated?
decreased ADAR2 –> increased calcium –> Akt pathway to promote cell proliferation and tumourigenesis.
Treatment: editing GluA2 Q/R can reverse the effects.
- When GluA2 Q/R is edited, or modified, it can decrease Ca2+ entry into cells and inhibit the Akt pathway, leading to decreased cell proliferation and tumor growth.
What type of assembly do P2X receptors have?
Trimeric assembly:
- 3 subunits with 2 TM helices
- Large extracellular domain
- 3 ATP molecules needed to open channel
- Widely expressed
- P2X1 - 7 subtypes of subunits
