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
Brugada Syndrome
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
Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)
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
