Signal Transduction - Ion Channels Flashcards
What does Ligand binding to a receptor cause?
Conformational change in the protein receptor
Apart from being embedded in the cell membrane, where can receptors be found?
Nucleus or cytoplasm
When the agonist binds to the receptor, what does this allow? (Pathway)
Confo change and the receptor can activate the effector ligand and cause a signal transduction within the cell
Are signal transduction pathways conserved in the body?
Yes
What are the 4 major signal transduction pathways?
Ion channel
GPCR
Tyrosine kinase linked receptors (TKLRs)
Nuclear/intracellular receptors
What type of signalling molecule (ligand) activate the nuclear receptors?
Lipophillic ligand
What are the 2 types of ion channels?
Ligand gated
Voltage gated
What is an example of a ligand gated ion channel?
GABAa
GABAa binds to its receptor and allows Cl- to enter the cell
Where does benzodiazapine bind on the GABAa receptor?
Binds to an allosteric binding site, increase the affinity of binding for GABA molecules
GABA more likely to bind channel more likely to open and influx of chloride into the cell
How does the BDZ cause sedation?
Cl- into cell
Causes a negative intracellular charge, making it harder for an ap to occur and therefore causes sedation
no AP firing, supress CNS
Does BDZ cause the GABAa channel to open for longer or more frequently?
More frequently
Do barbiturates cause the GABAa channel to open for longer or more frequently?
Open for longer
What is the normal charge of the intracellular cytoplasm?
Negative
What is the only way for ions to cross the cell membrane?
Ion channels
Only way cells can redistribute charge
What charge of molecule causes the firing of an AP?
Sodium (positive charge)
Depolarise cell
What is the charge of a cell at rest? (intracellular)
-70mV
polarised
Why does the cell becoming less negative (more positive) make it easier to stimulate an AP?
Less negative, so need less additional positive charge to cause a stimulus
Does benzodiazapine bind to the same or different (allosteric BS) from ligand?
Different
allosteric, increase affinity for GABA
hypopolarisation and harder to stimulate AP
What channels does LA inhibit?
Voltage gated sodium channels
block AP
What part of LA blocks the voltage gated sodium channel?
The amide side chain
What 2 forms can LA exist?
Non-ionised and iodised
From where do LA block sodium channels?
Penetrates the cell membrane in the non-ionised form (pass through cell), blocks channel in the ionised form from the inside (extra hydrogen)
What forms can LA pass the membrane and block the channel?
What does the balance of LA ionised and non-ionised depend on?
PH
