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Flashcards in ion channels 2 Deck (30):
1

IKto

1. – (Kv4.3 tetramer + KChiP2)
2. voltage-dependent inactivation

2

IKr

1. (HERG tetramer + miRP1)
2. “rapid” delayed rectifier

3

IKs

1. (KvLQT1 tetramer + minK)
2. “slow” delayed rectifier

4

Time-dependent cation current

1. If (or Ih)
2. (HCN tetramer)
3. Evoked by hyperpolarization
4. Na+ & K+ permeable
5. Erev ~ -30 mV

5

Inward Rectifier potassium currents

1. IK1
2. IKACh

6

IK1

(Kir tetramer)

7

IKACh

1. (GIRK tetramer)
2. Increased by activation of muscarinic receptors
3. slows pacemaking

8

Pacemaker Depol.

1. Turning on of If
2. Activation of ICa-T
3. Deact. of IKr & IKs

9

HERG is an

“anti-target” tested in preclinical evaluation of new drugs

10

HERG produces

Ikr

11

HERG is important for

duration of slow and fast APs

12

Reducing Ikr can cause

arrhythmias

13

HERG is blocked by

diverse compounds

14

in the heart, electrical activity functions to

1. Generates repetitive firing in specialized, “pacemaker” regions
2. Propagates within the myocardium and via specialized conductive pathways
3. Serves as a trigger for contraction of the myocardium

15

The cardiac action potential is the trigger for an

increase in the intracellular concentration of calcium ions, which, in turn, causes contraction of the myocardium.

16

pacemaker cells

initiate cardiac AP
slowly depolarize to threshold in the absence of extrinsic input

17

The rate at which a normal heart beats is controlled by

pacemaker cells in the sinoatrial node (SA node).

18

The SA node is a

1. cluster of small (7 μm diameter), round and spindle-shaped cells that contain few myofilaments.
2. automaticity
3. rhythmicity

19

automaticity

cells are spontaneously active

20

rhythmicity

will fire action potentials at a frequency of about 100/min

21

The SA node is innervated by

both sympathetic and parasympathetic axons.

Ongoing activity in the parasympathetic axons (parasympathetic tone) typically slows the rate at which cells in the SA node fire to 60-80 action potentials/min.

22

overdrive suppression

an action potential will spread to them from the SA node before they reach threshold on their own

23

ectopic pacemaker

Under abnormal circumstances these cells (or others, especially cells in damaged regions of the myocardium) can take over initiation of the heartbeat

24

Because heart rate is controlled by electrical activity of the SA node, the propagation of this activity to other regions of the heart has to occur such that

the two atria contract and relax in a coordinated fashion, that two ventricles contract and relax in a coordinated fashion, and that ventricular contraction occurs during atrial relaxation (and vice versa).

25

High Voltage activated (HVA) types

1. L type
2. neuronal

26

L type channels include

CaV1.1, CaV1.2, CaV1.3, CaV1.4

27

Neuronal channels include

CaV2.1, CaV2.2, CaV2.3

28

Low voltage activated (LVA) types

T type, which includes: Cav3.1, 3.2, 3.3

29

L-type calcium channels containing CaV1.2 are predominant in

ventricular and atrial myocardium and cells of the SA and AV nodes and conductive pathways.

30

SA nodal cells also express

L-type channels containing CaV1.3.