Cardiac ion channels + Action potentials

Question 1

Cardiac action potentials are initiated by?

Answer 1

pacemaker cells

Question 2

What controls the rate at which a normal heart beats?

Answer 2

Pacemaker cells in the sinoatrial node (SA node) which are innervated by sympathetic and parasympathetic axons

Question 3

Describe pacemaker cells

Answer 3

These cells are spontaneously active (automaticity) and will fire action potentials at a frequency of about 100/min (rhythmicity) for SA node and much lower for AV node.

Question 4

What slows the HR to 60-80 beats/min?

Answer 4

Parasympathetic tone

Question 5

What is overdrive suppression?

Answer 5

Cells in AV node fire less frequently than SA node, so they are driven by AP generated in SA node

Question 6

What is an ectopic pacemaker?

Answer 6

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

Question 7

How do cardiac cells allow for cell-to-cell propagation?

Answer 7

Gap junctions

Question 8

Where is the site that AP are propagated from SA node to ventricles?

Answer 8

AV node

Question 9

What are the relative speeds of APs in SA node, atria, AV node, purkinje fiber, ventricle

Answer 9

SA and AV node are slow, all else are fast

Question 10

Using membrane potential (Vm) and ion gradient (Nernst E) when does current flow into and out of cell?

Answer 10

If VmEion, current flows out of cell

Question 11

What is unique about Na and Ca channels?

Answer 11

They have an inactivation gate

Question 12

Which Ca channels are high voltage activated and which are low voltage activated? Where are these channels located

Answer 12

HVA: L-type (in ventricular and atrial myocardium and cells of the SA and AV nodes and conductive pathways) and neuronal
LVA: T-type (in SA node)

Question 13

Which channels have voltage dependent inactivation? Calcium dependent inactivation? Both?

Answer 13

VD alone: Na, Kto and T-type Ca channels
CD alone: none
Both: L-type Ca channel

Question 14

Which channels have time-dependent inactivation?

Answer 14

Ikr is rapid delayed rectifier

Iks is slow delayed rectifier

Question 15

What is Ik1? IkAch?

Answer 15

Ik1 is “inward rectifier” channel that readily conduct inward K current at potentials less than Ek
IkAch is current that increases in response to Ach acting on muscarinic receptors. Important for PNS slowing of SA node.

Question 16

What is If (Ib) current?

Answer 16

Channel is permeable to both Na and K. It is turned off at depolarized potentials and turned on at hyperpolarized potentials

Question 17

The categorization of cardiac action potentials as fast or slow is based on what? Which cells have fast AP? Which cells have slow AP?

Answer 17

Whether the initial upstroke is rapid or slow. Myocardial cells and cells of the rapid conduction pathways display fast action potentials. Pacemaker cells of SA node and AV node are slow

Question 18

In a fast AP, which ion channel/current causes phase 0?

Answer 18

entry of sodium ions (INa) through voltage-activated sodium channels.

Question 19

In a fast AP, which ion channel/current causes phase 1?

Answer 19

small, partial repolarization is produced by a combination of inactivation of sodium current and activation of a transient potassium current (IKto)

Question 20

In a fast AP, which ion channel/current causes phase 2?

Answer 20

Voltage-activated L-type Ca channels are open and influx of Ca is balanced by efflux of K (IKr and IKs)

Question 21

In a fast AP, which ion channel/current causes phase 3?

Answer 21

increasing activation of IKr and IKs and inactivation of ICa

Question 22

In a fast AP, which ion channel/current causes phase 4?

Answer 22

Inward rectifier IK1 holds cell near Ek (IKr and IKs are de-activated, and inactivation of INa and ICa is removed)

Question 23

What is the absolute and relative refractory periods?

Answer 23

Absolute: AP cant be initiated until most of Na inactivation is removed
Relative: threshold for second AP is elevated until repolarization is complete (complete removal of inactivation of INa and deactivation of IKr and IKs)

Question 24

How do cells with slow AP differ from cells with fast AP?

Answer 24

Pacemaker cells have reduced INa and little IK1; moreover, pacemaker cells express If and ICa-T which are essentially absent in myocardial cells

Question 25

In a slow AP, which ion channel/current causes phase 0?

Answer 25

Activation of ICa-T and ICa-L and is relatively slow owing to the absence of INa.

Question 26

In a slow AP, which ion channel/current causes phase 3?

Answer 26

Ikr and Iks

Question 27

In a slow AP, which ion channel/current causes phase 4?

Answer 27

If is induced by hyperpolarization. Aka pacemaker potential

Question 28

What is the importance of HERG in evaluation of new drugs?

Answer 28

Altered HERG (Ikr) function can disrupt normal cardiac electrical activity, so new drugs are tested to determine whether they block HERG channels