Ion channel diversity II Flashcards
Which part of the VGNa+ channel is voltage sensitive?
Fourth domain
Where does the pore sit in the VGNa+ channel?
between transmembrane region 5 and 6 in the first alpha subunit
Role of inactivation gate?
switches off the channel–> rapid requiring kinetics to terminte
Regulators of VGNa+ channel?
Phosphorylation–> regulate channel kinetics, desensitisation
Drugs can target sites as well
Evolution of VGNa+ and VGCa2+ channels?
Both arose from a common ancestor
What is the common ancestor of VGNa+ and VGCa2+ channels?
NaChBac–> bacterial VGNa+ channel
Structure of NaChBac?
Kind of like one of the 4 domains seen on the VGNa+ channel
How closely related are VGNa+ anc VGCa2+ channels?
1/2 AA changes can be the diff
Amounts of each channel (sodium, calcium, potassium)
Na=10
Ca=10
K=40
How are the 4 domains arranged in a VGNa+ channel?
Around a central pore
What creates the central pore in the VGNa+ channel?
P loop
What does the p loop/pore contain?
Selectivity filter
Role of selectivity filter in p loop?
Gives specificity to Na+
How many voltage sensor domains are there in a VGNa+ channel?
4
Where is the extracellular funnel?
Leading into the selectivity filter
Role of extracellular funnel?
Ions accumulate there before passage through the selectivity filter
Which specific part of the repeats are voltage sensing?
4 voltage sensing arginines in S4
Effect of resting membrane potential on argenines?
Inward force which pulls it into the membrane
Effect of inward force?
Pulls on linker which holds S6 domain in an upright position–> S6 domain causes closing of the channel
Order of things closing the VGNa+ channel?
Resting potential pulls arginines (in S4 domain) in
S4 domain is connected to S4-S5 linker which then hold S6 upright, closing the channe
Role of extracellular -ve cluster?
Senses electrical force into the channel
Which type of coupling holds the channel closed?
Electro-mechanical
Mechanism to open VG channels?
sliding helix ot helical twist
What is a gating cuttent?
Movement of +ve charge towards the outside, proceeds Na+ entry
Mechanism of VGNa+ inactivation?
Hinge lid mechanism
Effect of closing VGNa+ channel?
Prevents quick reopening, allowing recovery of ion gradients and return to resting membrane potential
What does inactivation of a VGNa+ channel limit?
Frequency of AP firing
What is VGNa+ channel inactivation sensed by?
4 AA motif (IFMT)
Where is the 4 AA motif (IFMT)?
3/4 linker (cytoplasmic loop) in the channel
