Cardiac Ion Channels, Action Potentials, & Conduction Flashcards
L-type Ca2+ channels
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
IKto Channels
K+ channels that produce a small, repolarization current following rapid depolarization of the fast myocardial action potential
IKr
Rapid K+ rectifier channel; responsible for plateau (2) and repolarization (3) phases of the mycardial action potential
IKs
Slow K+ rectifier channel; responsible for plateau (2) and repolarization (3) phases of the myocardial action potential
IK1
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
If
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
T-Type Ca2+ channels
Activated by weak depolarizations; expressed in the SA node
IKAch
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
Absolute refractory period
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
Relative refractory period
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
First degree AV block
Conduction delayed but all P waves conduct to the ventricles and are followed by R waves
Lengthening of PR interval
2nd degree AV block
Some P waves conduct to ventricles and are followed by R waves while others do not
3rd degree AV block
None of the P waves conduct to the ventricles, no P waves are followed by R waves; ventricular pacemaker takes over
Right bundle branch block
Depolarization has to go through regular contractile myocytes rather than through Purkinje fibers; causes QRS widening with delayed conduction to right ventricle
Left bundle branch block
Depolarization has to go through regular contractile myocytes rather than through Purkinje fibers; causes QRS widening with delayed conduction to Left ventricle
How do disturbances in cardiac conduction cause tachyarrhythmias? 3 mechanisms
- Abnormal re-entry
- Ectopic foci
- Triggered activity
Which L-type Ca2+ channel isoform predominates in the heart?
Cav1.2
Which RyR isoform predominates in the heart?
RyR2
Mechanism of cardiac EC coupling
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
SERCA2 pump
Located in SR membrane, pumps Ca2+ from the mycoplasma into the SR
Calsequestrin
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
NCX
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
4 targets of PKA
- LTCCs - increases amplitude of L-type Ca2+ current (trigger calcium); positive inotropic effect
- RyR2 - sensitizes RyR2 to lower levels of trigger Ca2+; positive inotropic effect
- Phospholamban - causes PLB to dissociate from SERCA, relieving its normal inhibition; positive inotropic & lusitropic effects
- Troponin - causes decreased affinity of Tn for Ca2+; positive lusitropic effect
Timothy Syndrome
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