cardiac ion channelopathies - LQTS

Question 1

what is a channelopathy?

Answer 1

group of disordered caused by defective ion channels

Question 2

how can channelopathies be aqquired?

Answer 2

GOF or LOF of channel

from congenital
aqquired from medicines
genetic/ epigenetic

Question 3

what could happen to the ion channels in channelopathy?
Name an example of a channelopathies

Answer 3

change in structure or function of protein

for example CF is a channelopathy of CFTR channel

Question 4

how can a channel ion go wrong?

Answer 4

from transcription -> translation -> PTM
reuptake and degradation

there are many steps involved in synthesis of functioning of a channel ion which can be subject to dysfunction

Question 5

which ion is responsible for ventricular depolarisation?
A Na
B Cl
C Ca
D K

Answer 5

sodium ions

Question 6

which ion is responsible for ventricular repolarisation?
A Na
B Cl
C Ca
D K

Answer 6

potassium ions

Question 7

which ion is responsible for LQTS?
A Na
B Cl
C Ca
D K

Answer 7

potasssium ion
reduced efflux

prolonging qt interval

Question 8

which ion channels defect is reponsible for LQTS 1?

Answer 8

KCNQ1 mutation is responsible for 50% of all LQTS cases

but also defects in KCNE1 contribute too

Question 9

what kind of current does KCNQ1 generate?

Answer 9

a slowly activating outwardly rectifying K+ curent

KCNE1 subunit is ESSENTIAL for this characteristic

Question 10

how does the ion channel in LQTS1 normally function (in an ECG?)

Answer 10

responsible for K+ efflux and balances out calcium influx in early repolarisation leading to a plateau

and eventually dominates leading to complete ventricular repolarisation

Question 11

how is the AP changed in LQTS1? Why?

Answer 11

as the KCNQ1 is mutated there is reduced potassium efflux

this prolongs the AP or result in extra after-depolarisations = long QT

Question 12

describe a potassisum channel (KCNQ1)

Answer 12

unlike Ca2+ and Na+, transmembrane multimeric protein

4 identical pore forming subunits
other auxillary subunits

Question 13

why is LQTS1 dangerous?

Answer 13

as the AP is delayed, the cardiac membrane remains refractory for longer (unable to respond or fire another AP)

this alters electrical and contractile activity of the heart

Question 14

what is the function of KCNE1?

Answer 14

accessory subunit of KCNQ1

can influence KCNQ1 electrophysiological behavior
> essential to generate functional (rectifying) K+ currents
> acts a chaperone/ helps with channel trafficking

Question 15

which part of the Potassium ion channel forms the pore?
> the specific structure

Answer 15

S5 and S6 have a linker region between them which folds and forms a pore

Question 16

which part of the ion channel is responsible for voltage sensing?

Answer 16

S4 subunit which has many postively charged amino acids

Question 17

how can hypertensive syndromes like Liddle’s syndrome link to LQTS?

Answer 17

symptoms of liddle is hypokalcemia which can increase risk of LQTS as low extracellular K reduces activity of the KCNQ1 channel

prolong the repolarisation and the QT interval

Question 18

what is the QT-interval? What does it represent on ECG?

Answer 18

represents the ventricular action potential, both depolarisation and repolarisation