Biophysical Properties of Nav1.5 Flashcards
what is Nav1.5
the pore-forming subunit of the voltage-gated sodium channel dominantly expressed in the myocardium
how many transmembrane segments does each domain of Nav1.5 have
6
how does Nav1.5 form a pore
4 homologous domains exist in the membrane and curl up to form a pore
role of Nav1.5 S4-5 linker chain
where the conformational change responsible for opening the pore occurs
responsible for ion selectivity
at rest, which gate of Nav1.5 is closed
where is this gate
M gate
sits towards the outside of the membrane
what causes the M gate of Nav1.5 to open
what is the result of this
membrane potential reaching threshold potential of -55mV
Na+ entry and depolarisation of the cell
what effect does depolarisation on the cell have on Nav1.5
causes a conformational change which which closes the H gate
what effect does repolarisation of the membrane have on Nav1.5
M gate closes
H gate re-opens
what is SCN5A
the gene that encodes Nav1.5
where does Nav1.5 tend to be expressed/localised
why are they located in these areas
in T tubules: proximity to sarcoplasmic reticulum
intercalated discs: allow polarisation changes to be sensed by neighbouring cells (so heart cells contract en masse)
examples of conditions caused by polymorphisms of SCN5A
- long QT syndrome
- Brugada syndrome
- early repolarisation syndrome
- congenital sick sinus syndrome
- familial atrial fibrillation
- sudden infant death syndrome
how many polymorphisms of SCN5A are there
> 200
what type of mutation causes type-3 long QT syndrome
gain of function mutation in SCN5A
ECG effects of long QT syndrome
ST segment elevation
prolonged QT interval
what type of mutation causes Brugada syndrome
loss of function mutation in SCN5A
