Cardiac Ion Channels & Action Potentials Flashcards Preview

CVPR Exam 1 > Cardiac Ion Channels & Action Potentials > Flashcards

Flashcards in Cardiac Ion Channels & Action Potentials Deck (51):
1

What are the three things that electrical activity does in the heart?



• Generates repetitive firing in specialized "pacemaker" regions
• Propagates within the myocardium and via specialized conductive pathways
• Serves as a trigger for contraction of the myocardium

2

What is meant by ectopic pacemakers?

• Whenever a region of the heart takes over initiation of the heartbeat from the SA node

3

What is meant by overdrive suppression?

• The phenomenon of SA node action potential propagation hitting the AV node before it spontaneously depolarizes on its own

4

What do the SA and AV node have in common?

• They both have automaticity and rhythmicity, but the AV node fires more slowly than does the SA node
• Thus, usually SA node action potential propagation hits the AV node before they spontaneously depolarize

5

100 beats/min is an "elevated" heart rate. So what makes the SA node fire more slowly most of the time?

• Parasympathetic tone, or ongoing activity in the parasympathetic axons
• Slows to 60-80 action potentials per minute
○ And thus the same beats per minute

6

What is meant by automaticity of the SA node?

• Spontaneously active cells that do not need extrinsic factors to fire

7

What is meant by rhytmicity of the SA node?

• The intrinsic firing frequency of about 100/min

8

What is the SA node?

• Sinoatrial node
• Cluster of small (7um diameter), round and spindle-shaped cells that contain few myofilaments
• Spontaneously active
• Fire at 100/min

9

What is special about pacemaker cells?

• They slowly depolarize to threshold in the ABSENCE of extrinsic input

10

What is the cardiac action potential a trigger for?

• The release of intracellular calcium and contraction of the myocardium

11

How does the action potential propagate through the heart?


• Starts in SA node, and specialized cells carry that action potential to the AV node
• Only the AV node is connected to the proper cells that propogate the action potential further to the ventricles (under normal circumstances)
• Gap junctions play a critical role in propogating an action potential throughout the atria or the ventricles
• The atria are insulated from the ventricles so the atria are coordinated separately from the ventricles

12

Why do the specialized cells connected to the AV node propogate action potentials more quickly than would gap junctions?

• They are large in diameter (30-70um instead of the normal 15um)
• Radius greatly increases speed of propogation

13

What is the principle subunit in the cardiac sodium channel?



• Nav 1.5

14

How many low voltage activated calcium channels did we discuss?

• One. T-type channels

15

How many high voltage activated calcium channels did we disucss?

• Two. L-type and neuronal

16

What are the three types of calcium channel we talked about?

• L-type
○ Important subunits in the "1"s, like Cav 1.1
○ High voltage activated
• Neuronal channels
○ Important subunits in the "2"s like Cav 2.1
○ High voltage activated
• T-type channels
○ Important subunits in the "3"s like Cav 3.1
○ LOW voltage activated

17

What channel is pretty similar to the sodium channel but has a whole bunch more important subunits?

• Calcium channel

18


What are the general characteristics of the cardiac sodium channel?

• They are similar to neurons and skelatal muscle sodium channels
• Depolarization leads to activation gate being swung away
• Inactivation gate will take it's place eventually

19

Where are you likely to find L-type calcium channels containing Cav1.2?





• They are predominant in ventricular and atrial myocardium
• Also in sells of SA and AV nodes
• Cells in conductive pathways

20

Where are you likely to see T-type calcium channels and why?

• LVA channels, activated by weaker depolarizations than those required for activation of HVA channels
• They activate and inactivate in response to depolarization much like a sodium channel BUT THEY ARE SLOWER
• You find them in the SA node and in the nervous system

21

What are the pharmacologic characteristics of L-type calcium channels?

• Blocked by dihydropyridines
• Nifedipine is the example used
• These are used as anti-hypertensive agents

22

What is meant by CDI when discussing channels

• Calcium dependent inactivation

23

What is meant by VDI when discussing channels?

• Voltage-dependent inactivation

24

What is special about L-type channels?

• They activate quite rapidly in response to depolarization and subsequntly inactivate in a manner dependent both on voltage and cytoplasmic calcium

25

What is different about the principle subunits found in potassium channels vs. sodium and calcium channels?


• They assemble as tetramers

26

What are I-K-1 channels ideally suited for?

• These channels are ideally suited for holding cells near Ek between action potentials without producing an outward current upon depolariation that would be energetically costly

27

What's up with the I-K-1 channel?

• The inward rectifier channel
• Not gated conventionally
• Conductance is steeply voltage dependent by cytoplasmic constituents
• Instantaneous rectification, meaning they readily conduct inward K current at potentials below Ek and only weakly pass outward K current at potentials slightly positive to Ek
• These channels are ideally suited for holding cells near Ek between action potentials without producing an outward current upon depolariation that would be energetically costly

28

What are the two potassium channels involved in inward rectifier potassium currents?

• I-K-1
• I-K-Ach

29

What is the slow delayed rectifier channel?

• I-K-a channel
• KVLQT1

30

What's up with the I-K-r channel?

• Rapid delayed rectifier

31

What is special about the I-K-to channel?

• Kv4.3 tetramer
• Depolarization causes both activation and inactivation on a time scale only slightly loswer than that of sodium

32

What is important about the I-K-Ach channel?


• Current is increased in response to acetylcholine acting on muscarinic receptors
○ G-protein-coupled receptors
• Important for parasympathetic tone
○ Slow pacemaker activity of SA node

33

What is different about the I-f and I-h channels?

• They are the same channel
• F = funny, h = hyperpolarized
• They are "off" at depolarized potentials and "on" at hyperpolarized potentials
• Permeable to Na and K
• Inactivation removed by hyperpolarization

34

The diagram for the fast cardiac action potential has 5 different currents shown through 5 different channels. Which are these and what are they showing?


• I-Na
○ Sodium current. Very fast and brief inward flow
• I-Ca-L
○ L-type calcium channels. Opesn after sodium channels cuase deploarization
○ Slower inactivation
○ Open through 0,1,2, close before 3
• I-K-to
○ Transient outward current the same time course as Na current
• I-K-r + I-K-s
○ Delayed rectifier current
○ Outward current open at 1 and peak right before 3
• I-K-1
○ Inward rectifier current
○ Outward postassium flow when membrane is hyperpolarized

35

What are the three different lines that make up the Slow cardiac action potential figure?

• I-Ca-T+L
○ Slow, slight influx of calcium until channels activated
○ Inward movement of calcium and slow inactivation
• I-f
○ Inward current until Calcium channels open, then it inactivates
○ Slowly increases inward current as calcium channels inactivate
• I-K-r+s
○ Delayed rectifier current
○ Slight outward current until calcium channels open, then larger outward current

36

What is "phase 0" of the cardiac action potential?



• Initial upstroke. Refers to fast and slow action potential figures

37

What happens after phase 1 in the fast cardiac action potential?

• Phase 2, or prolonged plateau
• Voltage activated L-type calcium channels are open
• Influx of calcium is approximately balanced by an efflux of potassium ions thorugh I-K-r+s
• Membrane potential is around 0mV during plateau

38

What happens after phase 0 in the fast cardiac action potential?

• Phase 1, or partial repolarization
• Produced by a combination of inactivation of sodium current and activation of a tansient postassium current
○ I-K-to

39

What does phase 0 of a fast cardiac potential look like?

• Rapid deploarization caused by entry of sodium ions through voltage-activated sodium channels
• Rapid upstroke of fast cardiac action potentials indicates the faster spatial propagation than is seen in slow action potentials

40

What causes phase 3 of the fast cardiac action potential and what is it?


• Phase 3 is the rapid repolarization phase
• Caused by inactivation of I-Ca (calcium channels and thus calcium current)
• Also by increasing activation of I-K-r+s or delayed rectifier channels

41

What channel is responsible for phase 4 of the fast cardiac action potential?

• The inward rectifier, I-K-1 is responsible for holding the membrane potential close to Ek
• The sodium and calcium channels are inactivated and the delayed rectifiers are also de-activated at this point

42

Why is a second action potential immediately following the first not really a concern?

• There is both an absolute and relative refractory period
• Absolute has to do with time taken to remove the inactivation of the sodium channels
• Relative refractory period means there is a higher threshold until I-K-r+s are deactivated and the sodium channels lose their inactivation

43

The pacemaker cells in the SA and AV node are missing what ion channels?

• Very reduced I-Na (sodium channels)
• Very little I-K-1 (inward rectifier channel)
• They also EXPRESS I-f and I-Ca-T channels, which are not present in other myocardial cells

44

What is important about HERG in testing preclinical new drugs?

• I-K-r has the HERG tetramer
• Important for repolarization of both fast and slow cardiac action potentials
• Messing this up is BAD
• It is easily messed up by unrelated compounds, so you always test a compound pre-clinically for HERG disruption

45

What other cellular process NOT surface ion channel-based plays a role in the rhythmicity of cardiac pacemaker potentials?

• Internal calcium release and the resultant movements of sodium and calcium via the NCX sodium/calcium exchanger
• Has to do with EC coupling and calcium movements

46

What does the "funny current" do?

• Plays a role in keeping membrane potential close to the reversal potential for I-f, = -30mV

47

Phase 4 in the slow cardiac acton potential?

• Slow deoploarization, "pacemaker potential"
• Brings cell back to threshold for the generation of another action potential

48

What's going on in phase 3 of the slow cardiac action potential?

• Balance between clacium current and delayed rectifier current (I-K-r+s)
• Repolarization occurs shortly after the peak of the acton potential
• Reploarization = phase 3

49

What is going on in phase 0 of the SLOW cardiac action potential?

• Activation of I-Ca-T channels and I-Ca-L channels
• This activation is relatively slow because of the lack of sodium channels

50

What phases of the fast cardiac action potential are present in the slow cardiac action potential?

• Phase 0
• Phase 3
• Phase 4
○ They are missing 1 and 2

51

What is the result of the differential ion channel expression in the pacemaker cells vs. the myocardial cells?

• They have no stable resing potential
• They produce repetitive slow action potentials