Cardiac Ion Channels, Action Potentials, & Conduction

Question 1

L-type Ca2+ channels

Answer 1

Voltage-activated Ca2+ channels

Allow influx of Ca2+ that is responsible for the plateau phase (2) of fast myocardial action potentials

Activate rapidly in response to depolarization and then inactivate

Question 2

IKto Channels

Answer 2

K+ channels that produce a small, repolarization current following rapid depolarization of the fast myocardial action potential

Question 3

IKr

Answer 3

Rapid K+ rectifier channel; responsible for plateau (2) and repolarization (3) phases of the mycardial action potential

Question 4

IKs

Answer 4

Slow K+ rectifier channel; responsible for plateau (2) and repolarization (3) phases of the myocardial action potential

Question 5

IK1

Answer 5

Inward rectifier K+ channel; readily conducts inward K+ current at potentials below Ek and only weakly passes outward K+ current at potentials positive to Ek; therefore responsible for maintenance of cell potential near Ek between depolarizations

Question 6

If

Answer 6

Responsible for conducting the “funny” Na2+ current that is responsible for the slow creep of membrane potential toward threshold between beats in automatic cells; induced by hyperpolarization

Question 7

T-Type Ca2+ channels

Answer 7

Activated by weak depolarizations; expressed in the SA node

Question 8

IKAch

Answer 8

K+ channels that increase their outward current in response to ACh acting on muscarinic receptors; important for the ability of parasympathetic nervous system to slow pacemaker activity of the SA node

Question 9

Absolute refractory period

Answer 9

The time during which a second action potential cannot be initiated, while most of the Na+ channels remain inactivated

On ECG, corresponds to the time from the Q wave to the peak of the T wave

Question 10

Relative refractory period

Answer 10

The time during which the threshold for production of a second action potential remains elevated, prior to complete removal of Na+ channel inactivation and deactivation of IKr and IKs

On ECG, corresponds to the latter half of the T wave

Question 11

First degree AV block

Answer 11

Conduction delayed but all P waves conduct to the ventricles and are followed by R waves

Lengthening of PR interval

Question 12

2nd degree AV block

Answer 12

Some P waves conduct to ventricles and are followed by R waves while others do not

Question 13

3rd degree AV block

Answer 13

None of the P waves conduct to the ventricles, no P waves are followed by R waves; ventricular pacemaker takes over

Question 14

Right bundle branch block

Answer 14

Depolarization has to go through regular contractile myocytes rather than through Purkinje fibers; causes QRS widening with delayed conduction to right ventricle

Question 15

Left bundle branch block

Answer 15

Depolarization has to go through regular contractile myocytes rather than through Purkinje fibers; causes QRS widening with delayed conduction to Left ventricle

Question 16

How do disturbances in cardiac conduction cause tachyarrhythmias? 3 mechanisms

Answer 16

1. Abnormal re-entry
2. Ectopic foci
3. Triggered activity

Question 17

Which L-type Ca2+ channel isoform predominates in the heart?

Answer 17

Cav1.2

Question 18

Which RyR isoform predominates in the heart?

Answer 18

RyR2

Question 19

Mechanism of cardiac EC coupling

Answer 19

Wave of depolarization triggers DHPR Ca2+ channel on the plasma membrane to open, allowing an influx of trigger Ca2+; trigger Ca2+ activates RyR2 on the SR to open, allowing a large flux of Ca2+ from the SR to the mycoplasma; Ca2+ activates contraction by binding to Tn-C on thin filaments

Question 20

SERCA2 pump

Answer 20

Located in SR membrane, pumps Ca2+ from the mycoplasma into the SR

Question 21

Calsequestrin

Answer 21

Low-affinity, Ca2+ binding buffer protein located in the SR of cardiomyocytes; keeps effective concentration of Ca2+ in the SR low to aid Ca2+ reuptake

Question 22

NCX

Answer 22

Located in plasma membrane and t-tubules of cardiomyocytes, pumps 1 Ca2+ out of the cell for every 3Na+ brought in

Runs backwards for a brief time during the action potential upstroke when Vm > Vr, supplying trigger Ca2+ to the activated cell

Question 23

4 targets of PKA

Answer 23

1. LTCCs - increases amplitude of L-type Ca2+ current (trigger calcium); positive inotropic effect
2. RyR2 - sensitizes RyR2 to lower levels of trigger Ca2+; positive inotropic effect
3. Phospholamban - causes PLB to dissociate from SERCA, relieving its normal inhibition; positive inotropic & lusitropic effects
4. Troponin - causes decreased affinity of Tn for Ca2+; positive lusitropic effect

Question 24

Timothy Syndrome

Answer 24

Caused by mutatiosn in the LTTC Cav1.2 which decreases voltage-dependent inactivation, leading to increased Ca2+ influx across an elongated action potential plateau

Patients display AV block, prolonged QT intervals, and episodes of ventricular tachycardia

Question 25

Brugada Syndrome

Answer 25

AKA “Sudden Unexplained Death Syndrome”

Caused by mutations of the cardiac sodium channel, Ikto channel, and ankyrin; the end result of these mutations is a large reduction in the magnitude of LTTC current (decreased duration of action potential plateau) with a shortened QT interval

Question 26

Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)

Answer 26

Caused by dominantly inherited mutations in RyR2 that increase the resting leak of Ca2+ out of the SR and/or render RyR2 more sensitive to activation by trigger Ca2+

B-adrenergic activity is pro-arrhythmogenic; it increases SR Ca2+ content as well as RyR sensitivity to Ca2+, resulting in inappropriate releases of Ca2+ that are not directly coupled to LTCC activation; extrusion of this Ca2+ via NCX results in inappropriate diastolic depolarizations that can trigger ectopic action potentials and arrhythmias