Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Ion channels and disease > L4 - B subunits > Flashcards

L4 - B subunits Flashcards

1
Q

what are Beta subunits?

A

small molecular weighted subunits, usually with 1TMD, which interact with the ion channel (alpha subunit) to change and regulate its properties

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

what happens in the cardiac AP?

A
  • fast influx of Na+ during depolarsation (when -70 Vm thresold reached)
  • platueu stage due to slow Ca2+ influx (NA+ decrease)
  • repolarisation due to fast K+ efflux (outward rectification) (PCa+ decrease)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

what causes K+ efflux in cardiac AP?

A

Ikr and Iks channels

balance between the 2 channels determines K+ efflux

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

give the properties of the Ikr channel?

A
  • rapid activation and inactivation (quicker than other K+ channels)
  • inward rectifier
  • delayed rectifier (slower than sodium channels)
  • KCNH1 (Herg1)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

give the properties of the Iks channel?

A
  • slow activation (in comparison to Ikr)
  • outward rectifier
  • delayed rectifier (compared to sodium channels)
  • KCNQ1 (Kvlqt1)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

what regulates KCNQ1?

A

-KCNE beta subunit family

KCNQ1 is the alpha subunit which forms an outwardly rectifying potassium channel (heart myocytes).

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

give the members of the KCNE family (B subunits which regulate KCNQ1 properties) (in heart myocytes)

A
  • KCNE1 (minK)
  • KCNE2 Mirp1
  • KCNE3 Mirp2
  • KCNE4 Mirp3
  • KCNE5 Mirp4
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

why is KCNE 1 called Mink?

A

it is small (minimal) so why called min

- wasnorgiginally thought to actually be a potassium channel (a subunit) so why called MinK

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

what effect does KCNE1 have on KCNQ1?

A
  • tested in hamster ovary cells
  • if KCNE1 is overexpressed (without KCNQ1) no current is generated as KCNE1 is not a channel.
  • if KCNE1 is overexpressed with KCNQ1 a bigger current is recorded but activation is slowed (time delay to reach a steady state)
  • rightward SHIFT IN VOLTAGE DEPENDENCE (need a more positive value for Iks channel to activate)
  • shows KCNE1 is regulating the activation of KCNQ1 (changes potential at which channels activate)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

what condition arises when KCNE1 is mutated?

A
  • long QT syndrome (LQT5)
  • higher risk of arrythmias and sudden death
  • repolarisation defect/delay
  • prolonged QT interval
  • apparent during excercise
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

what is the incidence of LQT?

A

1 in 10,000 to 1 in 15,000

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

what happens to the current in mutants which cause LQT5?

A

There is a smaller current and different time dependencies

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

what could be causing a smaller current?

A
  • gating issues
  • traffiking issues - less of channel at the membrane
  • issues in regulation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

what KCNE1 mutation effects gating?

A

L51H

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

what KCNE1 mutaitons impacts on traffiking and how do they know this?

A

L51H

  • tagged E1 with an antibody FLAG and looked for in permeabilised and non-permeabilised cells
  • WT E1 is present at the membrane
  • L51 H E1 is not present at the membrane in non-permeabilised cells but it seen in permeabilised cells so shows there is L51H present in the cells - but it is not being traffiked to the membrane.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

what is calnexin?

A

an ER marker (chaperone)

17
Q

where is WT KCNE1 seen?

A

in membrane and in ER (marked by overlap with calnexin)

18
Q

where is L51H found in the cell?

A

abundant in ER (hardly any/none in the membrane) - stuck in ER - not allowed to leave as incorrectly foled? (CNX cycle)- eventually sent for degradation via the ERAD pathway.

(so not traffiked past the ER)

19
Q

what does E1 do to Q1 location in the cell?

A
  • When E1 added to Q1 it started traffiking out of the ER (Q1 alone - lots in ER)
  • E1 chaperones Q1 to the membrane?
20
Q

what happens when L51H is added to KCNq1?

A

dont see much E1 or Q1 at the membrane - lots in ER

21
Q

why is Iks current smaller when E1 is mutated?

A
  • current is smaller as less Q1 channels are at the membrane due to a beta subunit/chaperone mutation in E1.
  • channels cannot traffic to the membrane efficiently
22
Q

why was Kv1.4 used in conjuction with E1 mutation (L51H)?

A

used as a control

  • when Kv1.4 used, the E1 mutation had no effect on the traffiking of Kv1.4 and Kv1.4 was still seen at the membrane normally.
  • this shows that KCNE1 + its mutation is specific to the properties of KCNQ1.
23
Q

How do mutations in KCNE1 cause LQT syndrome?

A
  • mutaitons in KCNE1 impact on the traffiking og KCNQ1- therefore there is less KCNQ1 at the cell membrane
  • this results in smaller Iks currents.
  • as there are smaller potassium currents, there is a slower efflux and slower outward rectification of poatssium ions from the heart myocyte.
  • This means repolarisation/inactivation takes longer to occur so the QT interval of the heart myocyte is extended beyond a normal range
  • this can cause arrythmias and a higher risk of sudden death.
24
Q

how is Kis regulated by cAMP?

A
  • sympathetic NS - increase heart rate - during exercise
  • beta adrenoceptors are activated which stimulate camp (PKA)
  • this causes activation of Iks (phosphoylation of Q1 by PKA)
  • this slows inactivation (of Iks channel)- get bigger currents
  • This increases the repolarisation rate
  • this increases heart rate
  • PPI removes P group (when don’t need high heart rate)

ocadaic acid inhibits PPI so dont get dephosphorylation - high currents + increased heart rate for longer

25
Q

what are the subunits alongside Q1?

A

E1
yotiao - allows PKA to come alongside Q1

  • PKA phosphorylates Q1
  • PPI dephosphorylates Q1
26
Q

what does camp dependence of Q1 channel depend on?

A

E1 needs to also be present

  • when ocodaic acid is added - there is little activaiton on Q1 when E1 is not present
27
Q

what happens in the D76N mutation?

A

the ability of E1/Q1 to respond to the sympathetic NS is lost
- unable to speed up heart rate during exercise

28
Q

what additional subunits - apart from E1 may there be alongside Q1?

A
  • yotiao
  • 14-3-3
  • KChips
  • KChap
  • KvB

Ion channels and disease (11 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions