CV - cardiac action potentials Flashcards
the three electrophysiologic types of cardiac cells capable of electrical excitation are ___________, ___________ and ___________.
pacemaker cells (SA node, AV node)
specialized rapidly conducting tissues (purkinje fibers)
ventricular and atrial muscle cells
cardiac action potentials are initiated by ___________ cells.
pacemaker
the rate at which a normal heart beats is controlled by pacemaker cells in the ___________ node.
sinoatrial (SA)
automaticity
spontaneously active, automatic
rhythmicity
spontaneous, repetitive, stable depolarization and depolarization of cells in cardiac muscle
the frequency of spontaneous action potentials fired by cells in the SA node is ___________ action potentials/minute.
100
parasympathetic tone
ongoing activity of parasympathetic axons involved in regulation of the action potentials in cardiac muscle
ongoing activity in the parasympathetic axons typically slows the rate at which cells in the SA node fire to ___________ action potentials/minute.
60-80
the frequency at which cells in the AV node fire action potentials is ___________ than that at which cells in the SA node fire.
lower
overdrive suppression
the higher frequency at which cells in the SA node fire suppresses the spontaneous activity of pacemaker cells at other sites, such as the AV node
ectopic pacemaker
under abnormal circumstances, especially after regions of the myocardium become damaged, pacemaker cells in regions of the heart outside the SA node can take over initiation of a heartbeat; may be benign at first and then progress to a pathologic process
L-type calcium channels containing Cav1.2 are predominant in ___________ cells of the SA and AV nodes and conductive pathways.
ventricular and atrial myocardium
L-type calcium channels are ___________ voltage activated.
high (HVA)
L-type calcium currents are blocked by ___________, which are used as anti-hypertensive agents.
dihydropurines (nifedipine)
T-type calcium channels are ___________ voltage activated.
low (LVA)
T-type calcium channels are expressed in the ___________ node and in the nervous system.
SA
“rapid” delayed rectifier potassium current
I_Kr
“slow” delayed rectifier potassium current
I_Ks
depolarization of a cell causes activation of the I_Kr and I-Ks currents on a time scale of ___________.
20-100 ms
I_K1
“inward rectifier” potassium current
“inward rectifier” potassium channels are suited for holding cells near ___________ between action potentials without producing outward current upon depolarization that would be energetically costly.
Ek
I_KACh is increased in response to ___________ acting on muscarinic receptors (G protein coupled receptors), and is important to enhance the ability of the ___________ nervous system to slow pacemaker activity of the ___________ node.
acetylcholine
parasympathetic
SA
the “funny” current (I_f or I_h) is called such because it is turned off at ___________ potentials and turned on at ___________ potentials.
depolarized
polarized
I_f is permeable to ___________ and ___________ ions.
Na+ and K+
___________ and ___________ cells display fast action potentials.
myocardial cells
cells of the rapid conduction pathways (purkinje fibers)
phase 0 of a fast cardiac action potential
rapid depolarization caused by the entry of sodium ions (I_Na) through voltage activated sodium channels
phase 1 of a fast cardiac action potential
small, partial depolarization produced by a combination of inactivation of sodium current and activation of a transient potassium current I_Kto
phase 2 of a fast cardiac action potential
prolonged plateau during which voltage-activated, L-type calcium channels are open and the influx of calcium ions is balanced by an efflux of potassium ions, keeping membrane potentials at a roughly constant level
phase 3 of a fast cardiac action potential
inactivation of I_Ca and increasing activation of I_Kr and I_Ks causes termination of the plateau and a rapid repolarization
phase 4 of a fast cardiac action potential
rapid repolarization in phase 3 results in deactivation of I_Kr and I_Ks and removal of inactivation of I_Na and I_Ca, keeping the cell held near Ek by I_K1
which cells display slow action potentials?
pacemaker cells of the SA and AV nodes
which currents are reduced in the slow cardiac action potentials of pacemaker cells?
I_Na and I_K1
which currents are expressed during by pacemaker cells but not by myocardial cells?
I_f and I_Ca-T
pacemaker potential
the slow depolarization during phase 4 of the slow cardiac action potential in pacemaker cells, which brings the cell back to threshold for generation of another action potential
the “funny current” I_f is induced by ___________.
hyperpolarization
although ion channels present in the plasma membrane of pacemaker cells provide a highly plausible mechanism for rhythmic firing, it has also been suggested that ___________ and the resultant movements of sodium and calcium via the ___________ play an important role in generating the pacemaker potential.
internal calcium release
NCX sodium/calcium exchanger
HERG is a component in the ___________ calcium current tetramer, and is important for ___________ of both fast and slow cardiac action potentials.
I_Kr
repolarization
why is HERG an important “anti-target” tested in preclinical evaluation of new drugs?
HERG channels are blocked by a wide variety of structurally unrelated compounds, and the altering of HERG function can disrupt normal cardiac electrical activity and lead to arrhythmias
what are the three main functions of electrical activity in the heart?
1 generates repetitive firing in specialized pacemaker regions
2 propagates within the myocardium and via specialized conductive pathways
3 serves as a trigger for contraction of the myocardium
what is the trigger for the increase in intracellular concentrations of calcium?
cardiac action potential
what happens when intracellular calcium increases?
myocardium contracts
what initiates cardiac action potentials?
pacemaker cells - spontaneous slow depolarization to threshold
what controls the rate of a normal heart?
pacemaker cells in the SA node
what is overdrive suppression?
the high frequency of the generation of action potentials by the SA node causes these action potentials to reach pacemaker cells in other areas of the heart before they are able to generate their own action potential, thus suppressing these action potentials
what is an ectopic pacemaker?
in abnormal heart function, especially damaged myocardial cells, pacemaker cells take over the initiation of a heartbeat
where in an normal heard does the electric signal pass from the atria to the ventricles?
atrioventricular (AV) node
how are ionic currents categorized? (4)
species of permanent ion(s)
kinetics
dependence on voltage or other activators
pharmacology
what is the principal subunit of the cardiac sodium channels?
Nav1.5
what are the two types of calcium channel?
high voltage activated (L-type and neuronal channels)
low voltage activated (T-type channels)
T/F L-type channels activate quickly in response to depolarization
true
what is the inactivation of L-type calcium channels dependent on?
voltage cytoplasmic calcium (calcium dependent inactivation, CDI)
where are T-type channels expressed?
SA node
nervous system
what are the two inward rectifier potassium channels?
I_K1 and I_KACh
what is the non-selective cation current?
this is the “funny” current (I_f) that is turned off at depolarized potentials and turned on at hyper polarized potentials
what characterizes phase 0 of the fast cardiac action potential?
rapid depolarization caused by entry of sodium ions (I_Na) through voltage-activated sodium channels
what characterizes phase 1 of the fast cardiac action potential?
small, partial repolarization caused by inactivated sodium current and activated transient potassium current
what characterizes phase 2 of the fast cardiac action potential?
prolonged plateau due to the opening of voltage-activated L-type calcium channels, with the influx of calcium (I_CaL) balanced by an efflux of potassium via the delayed rectifier potassium channels I_Kr and I_Ks
what characterizes phase 3 of the fast cardiac action potential?
rapid depolarization caused by the closing of I_CaL current channels and increase of I_Kr and I_Ks activity
what characterizes phase 4 of the fast cardiac action potential?
I_Kr and I_Ks are deactivated, and the inactivation of I_Na and I_Ca is removed; the cell is held near Ek by the inward rectifier
what causes phase 0 of the slow cardiac action potential?
increase in I_CaT and I_CaL currents due to the slow opening of calcium gates
what current likely plays an important role in the slow action potential?
funny current (I_f)
what are some other factors that are likely to be important in generating the pacemaker potential?
internal calcium release
movement of sodium and calcium by the NCX sodium/calcium exchanger
I_Kr is a tetramer of what protein?
HERG
why is I_Kr/HERG an important drug target?
HERG is involved in the repolarization of both slow and fast action potentials
until when does the threshold for a second action potential remain elevated?
until after depolarization is complete and there has been complete removal of inactivation of I_Na and deactivation of I_Kr and I_Ks
