Biophysical properties of Nav1.5 (Week 2) Flashcards

1
Q

what is Nav1.5

A

it is the alpha subunit of the cardiac sodium channel, encoded by the SCN5A gene.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

what is the cardiac sodium channel comprised of

A

a and beta subunit

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

what is Nav1.5 the pore-forming subunit of

A

the voltage-gated sodium channel expressed in the human myocardium

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

what are the sodium channels responsible for

A

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.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

what is the resting membrane potential

A

-70 millivolts, this negative charge is maintained by the distribution of ions across the cell membrane.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

explain the closed state (resting)

A

At the resting membrane potential, Nav1.5 channels are closed. In this state, the channel is not conducting sodium ions.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

explain the activation

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

explain inactivation

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

explain recovery from inactivation

A

the inactivated Nav1.5 channels transition to a closed, non-inactivated state. This process is known as recovery from inactivation.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

which gene is Nav1.5 encoded by

A

SCN5A

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

what are some genetic polymorphisms of SCN5A

A

Long QT syndrome (LQTS)
Brugada syndrome (BrS)
Early repolarisation syndrome
Congenital sick sinus syndrome
Familial atrial fibrillation
Sudden infant death syndrome

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

which type of LQTS is caused by the SCN5A gene

A

type 3

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

what does LQTS do

A

prolongs action potential duration (APD) and therefore, QT interval

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

explain brugadas syndrome

A

BrS type 1 caused by loss=of-function, mutations in SCN5A

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

name some optical mapping techniques for cardiac electrophysiology

A

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.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

what are some problems with anti-arrythmic drugs

A

they often have narrow therapeutic window

can cause pro-arrhythmia… some of which can be explained by understanding more about polymorphisms or biophysical properties of SCN5A

17
Q

point of mutation in SCN5A

A

point of mutation in the C-terminus of SCN5A alpha subunit can decrease sensitivity to flecainide

18
Q

what does brugadas syndrome do

A

genetic disorder that affects the heart’s electrical system, increasing the risk of serious heart rythme disturbances.

19
Q

what do

A
19
Q
A
20
Q
A