Lecture 8- Ligand gated ion channels Flashcards
What are two key features of ion channels?
- Gating mechanism- ligand or voltage
2. Ion selectivity of the pore
How are p loops formed and what is there function?
Subunits come together with the pore in the centre. P loops between two TMs create a highly selective filter.
How is a ion channel gate created and what is the function of it?
On the cytoplasmic side, the TMs are closely packed creating a gate that blocks ion passage
What part of voltage gated ion channels control gating?
The voltage sensing domain
When is a voltage sensitive K+ channel open and closed?
Negative membrane potential is sensed by S4 keeps gate closed. If membrane depolarises, S4 moved and gate opens.
When/how are voltage gated channels inactivated?
Channels are inactive when inactivating peptide swings into place blocking the pore.
What is a similarity and difference between TRP channel and voltage gated channels?
Channels share common structural features but TRP channels have evolved to sense chemical and physical stimuli
How are ligand gated ion channel gated?
Gated by chemical transmitters
Describe the structure of cyclic nucleotide gated channels
- A tetramer
- S5/6 alpha helical domains lining central pore p loop controlling filter
- Added regulatory domains to the intracellular N and C terminals
- Cyclic nucleotide binding domain on intracellular C terminal opens pore permeable to Na+/Ca+
- Ligand must bind to 3/4 sites for channel to open
- Negative feedback provided by calcium binding to N terminal associated calmodulin
Describe the structure of P2X channels
- Gated by the binding of ATP
- Trimeric assembly to form the channel
- ATP binds to pockets of the extracellular face of the channel
What is a homomeric ion channel?
The same protein subunits come together to create a functional channel
What is a heteromeric ion channel?
Different subunits come together to create a functional channel
Give an example of a pentameric, tetrametic and trimeric ligand gated ion channel.
- Pentameric: nicotinic and gabaergic receptor
- Tetrameric: glutamatergic receptor
- Trimeric: purinergic receptor
Mutations in what cause ADNFLE?
Mutations in nAChR subunits
What do voltage gated ion channels and ligand gated ion channels work together to control?
Control the excitability and function of muscle and neurons