The Voltage-gated Potassium Channel family Flashcards Preview

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Flashcards in The Voltage-gated Potassium Channel family Deck (75)
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1
Q

Name the 3 physiological functions that the potassium channels contribute to?

A
  1. Control of cell volume. 2. Control of membrane potential and cell excitability. 3. Secretion of salts, hormones & neurotransmitters.
2
Q

Name the 5 regulators of the potassium channels activity?

A
  1. Numerous hormones & transmitters. 2. Voltage across membrane. 3. Conc. of calcium or ATP in cytoplasm. 4. Kinases and phophatases. 5. G-proteins
3
Q

Name the 3 structures of the potassium channels?

A
  1. 6 transmembrane one-pore 2. Two transmembrane one-pore 3. Four transmembrane two-pore
4
Q

Properties of the 6-transmembrane segment potassium channels?

A
  1. alpha subunit similar in shape to the sodium and calcium channels. 2. Contains S4 voltage sensor and P region.
5
Q

Name the four channels that are part of the 6-transmembrane segment family?

A
  1. hERG channels. 2. Voltage-activated potassium channels. 3. Calcium activated potassium channels. 4. KCNQ channels
6
Q

What is the role of the voltage-activated potassium channels?

A

Responsible for shaping of the action potential.

7
Q

Name the main two types of voltage-activated potassium channels?

A
  1. Inactivating ‘A’ type. 2. Non-inactivating
8
Q

Properties of the inactivating ‘A’ type of voltage-activated potassium channels?

A

Display rapid inactivation following opening. Ball and chain form of inactivation

9
Q

Properties of the non-inactivating type of voltage-activated potassium channels?

A

Slow inactivation.

10
Q

Describe the “ball and chain” form of inactivation?

A

First 20 amino acids forms compact hydrophobic charged surface domains which plugs the channel from the inside. Prevents potassium efflux

11
Q

Describe the properties of the N-type inactivation?

A

Ball and chain inactivation mechanism.

12
Q

Where is the ball made from the ball and chain inactivation?

A

Set of amino acids in the S4-S5 loop.

13
Q

What controls the activity of the potassium channel?

A

Controlled by the conc. of cytoplasmic calcium. Important in limiting calcium entry and neuronal excitability.

14
Q

Name the 3 subtypes of calcium-activated potassium channels?

A
  1. Large conductance (maxi-K) 2. Intermediate (IK) conductance. 3. Small (SK) conductance.
15
Q

What channel is important for the slow afterhyperpolarisation observed after AP discharge?

A

Small conductance channels are responsible for this.

16
Q

Where are maxi-K channels expressed?

A

Ubiquitously (found everywhere) Help shape APs in neurones and regulate transmitter release. In smooth muscle: regulate contractile activity and tone.

17
Q

What controls the opening of maxi-K channels?

A

Transmembrane voltage as they are voltage-dependent.

18
Q

What is the activation of maxi-K channels dependent on?

A

The intracellular calcium conc. The more calcium conc. in the cell: the less electrical energy is needed to open it.

19
Q

Describe the beta and alpha subunits of the maxi-K channel?

A

beta: 2 transmembrane domians. Alpha: 6.

20
Q

What part of the alpha subunit is important for the function of the maxi-k channel?

A

The long COOH terminus

21
Q

What gene encodes for the Maxi-K alpha subunit?

A

Slo gene.

22
Q

What part is unique to maxi-K channels?

A

SO region

23
Q

Name the 4 types of beta subunits?

A

b1-4

24
Q

Role of the beta subunits in the maxi-K channel?

A

Alter sensitivity to calcium and voltage, activation kinetics.

25
Q

What terminal is required for beta subunit modulation?

A

S0/N terminal

26
Q

Where are maxi-K channels most abundant?

A

In CNS and smooth muscle.

27
Q

Name the two forms of gating for the maxi-K channel?

A

Voltage-gating and ligand-gating domains. 2 independent sensing mechanisms

28
Q

What part of the channel acts as the voltage sensor?

A

S4 region

29
Q

What part of the channel acts as the ligand gating?

A

Specialised structures present in the C-terminal region of the protein

30
Q

Define the role of the RCK domain?

A

Regulators of conductance of potassium. Contribute to binding of intracellular ligand

31
Q

Name the hydrophilic domains?

A

S9 and 10 of the COOH tail.

32
Q

What part of the COOH tail binds calcium?

A

Calcium bowl. Contains a series of negatively charged residues.

33
Q

What part of the COOH tail senses voltage?

A

S7 and 8 domain (RCK)

34
Q

How does the calcium bowl help in the calcium sensing of the maxi-K channels?

A

Calcium bowl interacts with the RCK domain to confer calcium sensing.

35
Q

How to increase the probability of the maxi-K channel opening?

A

Increasing intracellular calcium increases the opening force (calcium bowl + RCK domain). Voltage sensor adds to this force on the gates (S4 domain) and increases channel open probability.

36
Q

Loss of beta 1 subunit of the maxi-K correlates with what?

A

hypertension. Maxi-K is less calcium sensitive- increased arterial tone and BP.

37
Q

Maxi-K channels importance in VSM relaxation?

A

Calcium released by receptors causes local increase in calcium conc. Activates BK channels- K efflux. Hyperpolarisation: Initial depolarisation and contraction. Vascular smooth muscle relaxes.

38
Q

Maxi-K channels importance in neuronal excitability?

A

Present at high levels in axon terminals, somas and dendrites. Activated by increased intracellular calcium- profoundly depresses excitability.

39
Q

Properties of the two transmembrane domain potassium channels?

A

One pore family. Consist of the inward rectifiers. Conduct potassium current more in the inward direction than the outward. Help set RMP

40
Q

Properties of the four transmembrane domain potassium channels?

A

Two pore family. Weak inward rectifiers. Most abundant class. Act as background channels. Help set RMP.

41
Q

How many subunits are needed to form a functional channel of TREK1?

A

Only need 2 subunits. As they contain two ‘P’ loops

42
Q

K2p channel opening properties?

A

Constitutively open at rest. Contribute to RMP.

43
Q

Name the factors that control TREK1 channel activity?

A

Numerous cellular factors such as voltage.

44
Q

The role TREK1 plays in the body?

A

Neuronal background channel. Single integrators- response to many inputs mechanical deformation.

45
Q

How do you inhibit TREK1 channels opening?

A

Through phosphoryation at intracellular sites via PKC and PKA.

46
Q

Name the two types of anaesthetic agents that open TREK1?

A

Various volatile and gaseous anaesthetics agents.

47
Q

Where are the TREK1 channels expressed in within the body?

A

Highly expressed in the brain.

48
Q

Name the 5 different stimuli used to open the TREK1 channel?

A
  1. Pressure 2. Heat 3. Voltage 4. Anaesthetics and lipids. 5. pH
49
Q

Name the 3 different developmental areas that TREK1 is an attractive target for?

A
  1. New analgesics. 2. Neuroprotective agents. 3. Antidepressant drugs.
50
Q

Name the 4 openers of TREK1?

A
  1. Anaesthetics 2. Polyunsaturated fatty acids. 3. Lysophospholipids. 4. Riluzole.
51
Q

What happens in the presynaptics terminals when TREK1 channels are opened?

A

Closes voltage activated calcium channels. Decreasing the release of neurotoxic glutamate.

52
Q

What happens in the postsynaptics terminals when TREK1 channels are opened?

A

Hyperpolarises cell and increases NMDA receptor. Magnesium is used to block the channel- reducing excitotoxicity.

53
Q

Properties of the Kir 6.x channel?

A

Part of the K ir family of channels. This + a regulatory subunit = the SUR receptor. Activity inhibited by intracellular ATP.

54
Q

Name the two genes that encode for the Kir 6.x channel?

A

Kir 6.1 and Kir 6.2

55
Q

Role of the K atp channels?

A

Act to couple cellular metabolism and electrical activity. Responds to ATP levels

56
Q

Name the two functions of the K ATP channels?

A
  1. Stress sensing eg. skeletal, cardiac 2. Glucose sensing eg. pancreatic b-cells
57
Q

What happens to the K ATP channel when the ATP level is high?

A

The level of ATP is high inside the cell. Receptor closes.

58
Q

What happens to the K ATP channel when the ATP level is low?

A

The receptor opens.

59
Q

How does the K ATP channel work as a stress sensor?

A

These channels are closed under normal physiological conditions. Opens under metabolic stress (eg. hypoglycemia)

60
Q

What happens to the RMP when K ATP channels are open ?

A

Results in hyper polarisation of the RMP.

61
Q

How does the K ATP channel work as a glucose-sensor?

A

In these glucose-sensing cells the K ATP channels are partially open under physiological conditions and contribute to the RMP. Increase in glucose conc. increases intracellular ATP conc. and closes these channels. Results: increase in glucose conc. = cell depolarisation.

62
Q

Describe how the beta cells are at rest?

A

K ATP channels are open and the cell is at RMP. Low glucose levels outside: low ATP inside the cell: KATP channel open: Voltage gated calcium channels open: no insulin release.

63
Q

Describe what happens to the beta cells when there is an increase in glucose extracellularly?

A

GLUT transporter transports the glucose inside the cell. Increase in ATP- KATP channels closed- cell depolarisation- voltage gated calcium channels open- insulin released

64
Q

Describe the properties of the inhibitors of KATP channels?

A

Sylphonylureas. Increase tolbutamide and glibenchamide

65
Q

Sylphonylureas use?

A

As inhibitors of the KATP channels. Blockers

66
Q

Describe the properties of the activators of KATP channels?

A

Act on these channels to open them. Termed as potassium channel openers (KCOs) eg, cromakalim, pinacidil, minoxidil and diazoxide

67
Q

Use of diazoxide?

A

Used to decrease insulin secretion from beta-cells

68
Q

Use of the majority of KCOs?

A

Used to relax smooth muscle and testing for a variety of conditions such as hypertension, bladder overactivity. Also useful as cardioprotective and neuroprotective agents

69
Q

How does the G-protein couple to K channels?

A

Directly. G-proteins bind to the muscarinic ACh receptor and thus opens the potassium channels

70
Q

Properties of Long-QT syndrome?

A

Inherited genetic disorder. Characterised by prolonged or delayed ventricular repolarisation. Reduced function of certain voltage-gated potassium channel genes.

71
Q

Properties of epilepsy with respects to potassium channels?

A

Mutations leading to decreased expression/function of voltage-gated potassium channels.

72
Q

Properties of neurodegenerative conditions with respects to potassium channels?

A

Mutations in the Kir 3.2 Death of dopamine neurones.

73
Q

Properties of hyperinsulinemia of infancy?

A

Enhanced insulin secretion occurs. Leads to hypoglycaemia, coma and severe brain damage. Multiple mutations associated with K ATP channel

74
Q

Properties of diabetes (Type 2)?

A

Activating mutations in Kir 6.2 with decreased insulin secretion from pancreatic beta cells.

75
Q

Describe the cardiac action potential?

A

Stage 4: resting at -96mV. Stage 0: sodium in rapidly. Stage 1: potassium and chlorine out Stage 2: calcium in, potassium out Stage 3: potassium out.