Biophysical properties of Nav1.5 (Week 2) Flashcards
what is Nav1.5
it is the alpha subunit of the cardiac sodium channel, encoded by the SCN5A gene.
what is the cardiac sodium channel comprised of
a and beta subunit
what is Nav1.5 the pore-forming subunit of
the voltage-gated sodium channel expressed in the human myocardium
what are the sodium channels responsible for
rapid depolarisation phase of the cardiac action potential which is important in maintaining a steady heart rate.
Nav1.5 allows for the rapid influx of Na+ ions into cardiac cells during this depolarisation phase leading to the generation of an action potential.
what is the resting membrane potential
-70 millivolts, this negative charge is maintained by the distribution of ions across the cell membrane.
explain the closed state (resting)
At the resting membrane potential, Nav1.5 channels are closed. In this state, the channel is not conducting sodium ions.
explain the activation
membrane potential depolarises (becomes more positive) Nav1.5 channels undergo activation, channels open in response to depolarisation, there is then an influx of sodium ions
explain inactivation
causes a conformational change that closes the channel even though the membrane potential remains depolarised. Inactivation important to prevent continuous flow of sodium ions and allows cell to reset for next action potential
explain recovery from inactivation
the inactivated Nav1.5 channels transition to a closed, non-inactivated state. This process is known as recovery from inactivation.
which gene is Nav1.5 encoded by
SCN5A
what are some genetic polymorphisms of SCN5A
Long QT syndrome (LQTS)
Brugada syndrome (BrS)
Early repolarisation syndrome
Congenital sick sinus syndrome
Familial atrial fibrillation
Sudden infant death syndrome
which type of LQTS is caused by the SCN5A gene
type 3
what does LQTS do
prolongs action potential duration (APD) and therefore, QT interval
explain brugadas syndrome
BrS type 1 caused by loss=of-function, mutations in SCN5A
name some optical mapping techniques for cardiac electrophysiology
Flourecent indicators: Fluorescence-technique using potentiometric dyes in whole tissues/ hearts to permit quantification of local/regional or global changes in electrophysiology in paced specimens
Illumination and imaging: The tissue is illuminated with a light source that excites the fluorescent dye. The emitted fluorescence is then captured using a high speed camera or other imaging system.