NaV1.5

Question 1

What is NaV1.5?

Answer 1

voltage batted sodium channel found in cardiac muscle, encoded by the SCN5A and is responsible for generating action potentials in cardiac cells

Question 2

What is the main function of NaV1.5 in cardiac cells?

Answer 2

opens in response to depolarisation allowing an influx of sodium into the cell which triggers rapid depolarisation initiating action potential in cardiac cells

Question 3

What is the resting membrane potential threshold for NaV1.5 activation?

Answer 3

-65 to -55mV

Question 4

What is the role and location of the inactivation gate in NaV1.5?

Answer 4

primarily formed by the intracellular loop between domains III and IV, blocks the channel after activation, ensuring that sodium entry is brief

Question 5

What is the selectivity filter of NaV1.5, and how does it work?

Answer 5

is formed by the pore loop segments between domains 5 and 6, allowing selective permeability to Na+ ions while excluding other ions

Question 6

What is the effect of mutations in NaV1.5 on cardiac function?

Answer 6

cardiac arrhythmias

Question 7

How do drugs like lidocaine interact with NaV1.5?

Answer 7

Lidocaine and other local anesthetics block NaV1.5 by binding to its pore in the inactivated state, reducing sodium influx and decreasing excitability

Question 8

What is the conductance of NaV1.5 channels for sodium ions?

Answer 8

high conductance

Question 9

How does NaV1.5 inactivation affect cardiac refractory periods?

Answer 9

defines refractory period

Question 10

What are some common cardiac conditions associated with SCN5A polymorphisms?

Answer 10

brugada syndrome
long QT syndrome

Question 11

How do SCN5A polymorphisms contribute to Brugada syndrome?

Answer 11

loss-of-function mutation
leads to arrhythmias

Question 12

What is the role of SCN5A polymorphisms in Long QT syndrome type 3 (LQT3)?

Answer 12

gain-of-function mutation
causes prolong Na influx and extended QT interval
prolongs action potential

Question 13

How do SCN5A polymorphisms influence response to sodium channel blockers?

Answer 13

Some SCN5A loss-of-function mutations are sensitive to sodium channel blockers, which can exacerbate conduction issues

Question 14

which gene has recently been discovered as a possible cause of brugada syndrome

Answer 14

MAPRE2

Question 15

What is the patch-clamp technique, and how is it used in cardiac electrophysiology?

Answer 15

The patch-clamp technique allows for the recording of ionic currents through individual ion channels in isolated cardiomyocytes. It can measure voltage-gated sodium, calcium, and potassium currents, providing insights into channel function and action potential properties

Question 16

What is optical mapping, and how is it used in cardiac electrophysiology?

Answer 16

Optical mapping involves using fluorescent dyes to visualize electrical activity across cardiac tissue. Changes in fluorescence correlate with voltage changes, allowing for the measurement of action potential propagation and arrhythmias in cardiac tissue.

Question 17

a point mutation in the C-terminus of SCN5A α subunit
can decrease sensitivity to

Answer 17

flecainide

Question 18

heterozygous point mutation in SCN5A is associated with

Answer 18

familial AF

Question 19

name some anti arrhythmic drugs

Answer 19

propafenone
flecainide

Question 20

The selectivity filter of sodium channels, including Nav1.5, is primarily formed by a ___________ charged loop

Answer 20

Negatively

Question 21

what acts as the voltage sensor

Answer 21

S4 segment