Ion Channels Flashcards
3 main functional features of ion channels
Gate (pore opens & closes)
Conduct (ions move across membrane down electrochemical gradient)
Select (only allow certain ions to move through pore)
2 groups of the ion channel superfamily
Pore-loop channels
Miscellaneous
Channelopathies
Diseases caused by ion channel dysfunction
Ligand-gated ion channels - Nicotinic acetylcholine receptor (AChR) structure
Ring of 5 subunits
3 domains -> N terminal extracellular ligand binding domain, membrane-spanning pore, intracellular domain
Conduct a variety of cations but no anions
Ligand-gated ion channels - Nicotinic acetylcholine receptor (AChR) action
ACh binding causes local disturbance, leading to large-scale mechanical twisting of 2 alpha subunits, which parts the gate in the pore
C loop moves a considerable distance, causing rotation of beta strands that’s transmitted through the subunit to residues near the transmembrane domain
Voltage-gated ion channels example
Potassium channel
Potassium channel resting potential
Positively-charged residues in the voltage sensor domain are attracted to the negative intracellular membrane charge at resting potential (~-70mV)
Potassium channels depolarised
Voltage sensor translocates across membrane in response to depolarisation; channel open
Potassium channel opening process
Movement of voltage sensor pulls on linker, changing the positioning of the pore-lining helices and opening the pore
3 categories of ion channel selectivity
Non-selective -> (some) gap junction channels
Cation/anion selective -> (Cys-loop receptors)
Specific ion
What are gap junction channels?
Occur at specialised sites for INTERcellular communication & mediate passage of ions, metabolites, and small cell signalling molecules
How are gap junctions formed?
By docking 2 hemichannels (or connexons) on the cellular membrane; each connexon is composed of 6 transmembrane proteins called connexins
Connexins
Connexins contain 4 membrane-spanning domains, 2 extracellular loops, N and C termini intracellular
In humans there are at least 21 connexin family members
Gap junctions are formed of different connexin isoforms
Gap junction channels functions
‘molecular sieves’
Discriminate largely based on size, but also charge for SOME connexins
Cys-loop receptors - acetylcholine receptors (AChR)
Conduct a variety of cations but exclude anions
Electrostatic filter screening out ions of the wrong shape and size
Ion-specific channels - potassium channel
Transmembrane helices form ice cream cone shape
Selectivity filter formed by residues in the P-loop
Selectivity filter lined by backbone carbonyl oxygen atoms with side chains of the amino acids pointing away from the pore
