ion channels 3

Question 1

L-type channels functions:

Answer 1

1. activate quite rapidly in response to depolarization
2. inactivation dependent on both voltage (voltage-dependent inactivation, VDI) and cytoplasmic calcium (calcium-dependent inactivation, CDI).
3. also expressed in smooth and skeletal muscle and NS

Question 2

L-type calcium currents (ICa-L) are blocked by

Answer 2

dihydropyridines (nifedipine, for example), which are used as anti-hypertensive agents.

Question 3

T-type channels are described as “LVA” because they are

Answer 3

activated by weaker depolarizations than those required for activation of HVA channels.

Question 4

T-type calcium currents (ICa-T) function:

Answer 4

activate and then inactivate in response to depolarization (with a time course similar to, but slower than, sodium currents)

Question 5

T-type channels are expressed in

Answer 5

the SA node and in the nervous system.

Question 6

the principle subunits of

potassium channels assemble as:

Answer 6

tetramers

Question 7

IKACh: This current (GIRK tetramer) is increased in response to:

This mechanism is important for:

Answer 7

acetylcholine acting on muscarinic receptors (G-protein coupled receptors).

the ability of the parasympathetic nervous system to slow pacemaker activity of the SA node.

Question 8

Non selective (If) is activated at

Answer 8

both depolarized and hyperpolarized potentials.

Question 9

Non selective (If) is inactivated at

Answer 9

depolarized potentials

Question 10

If plays an important role in

Answer 10

pacemaking by SA nodal cells.

Question 11

Myocardial cells and cells of the rapid conduction pathways display ____

Answer 11

fast action potentials.

Question 12

Fast cardiac AP: phase 0

Answer 12

The initial upstroke (phase 0) of a fast cardiac action potential consists of a rapid depolarization caused by the entry of sodium ions (INa) through voltage- activated sodium channels.

Question 13

The______ of fast cardiac action potentials is an indicator of the much faster spatial propagation than occurs for slow action potentials.

Answer 13

rapid upstroke

Question 14

Fast cardiac AP: phase 1

Answer 14

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

Question 15

Fast cardiac AP: phase 2

Answer 15

1. prolonged plateau, during which voltage-activated, L-type calcium channels are open.
2. The influx of calcium ions (ICa-L) is approximately balanced by an efflux of potassium ions (IKr and IKs) via delayed rectifier channels so that membrane potential remains at a roughly constant level (near 0 mV)

Question 16

Fast cardiac AP: phase 3

Answer 16

1. The combination of inactivation of (ICa) and increasing activation of IKr and IKs causes termination of the plateau by a rapid repolarization
2. IKr and IKs are de-activated, and inactivation of INa and ICa is removed;

Question 17

Fast cardiac AP: phase 4

Answer 17

the cell is held near EK (phase 4) by the inward rectifier (IK1).

Question 18

absolute refractory period

Answer 18

a second action potential cannot be initiated until most of the inactivation of INa is removed (during the repolarizing phase)

cannot happen no matter what

Question 19

relative refractory period

Answer 19

the threshold for a second action potential remains elevated until after repolarization is complete (complete removal of inactivation of INa and deactivation of IKr and IKs has occurred)

Can happen, but needs more

Question 20

pacemaker cells have

Answer 20

1. reduced INa and little IK1

2. pacemaker cells express If and ICa-T which are absent in myocardial cells.

Question 21

slow cardiac AP phase 0

Answer 21

The upstroke (phase 0) is attributable to activation of ICa-T and ICa-L and is relatively slow owing to the absence of INa.

Question 22

slow cardiac AP phase 1

Answer 22

NO the partial repolarization

Question 23

slow cardiac AP phase 2

Answer 23

There is NO prolonged plateau, that is characteristic of fast action potentials.

Question 24

slow cardiac AP phase 3

Answer 24

the balance between ICa and delayed rectifier current (IKr and IKs) is such that repolarization (phase 3) occurs shortly after the peak of the action potential.

Question 25

slow cardiac AP phase 4

Answer 25

the repolarization is followed by a slow depolarization (the “pacemaker potential”) during phase 4, which brings the cell back to threshold for the generation of another action potential.

Question 26

one contribution to slow cardiac AP is

Answer 26

the funny current (If) which is induced by hyperpolarization.

Question 27

Induction of If allows

Answer 27

cation fluxes (sodium and to a slightly lesser extent potassium) which drive voltage towards the reversal potential of If (-30 mV).

Question 28

The pacemaker depolarization during phase 4 of slow cardiac action potentials is also facilitated by

Answer 28

the slow deactivation of IKr and IKs, and by activation of LVA Ca2+ current (ICa-T).

Question 29

____, ___ and ___ play an important role in generating the pacemaker potential.

Answer 29

1. internal calcium release
2. the resultant movements of sodium
3. calcium via the NCX sodium/calcium exchanger