Cardiac Excitation and Contraction I Flashcards
Cardiac output vs Stroke volume vs Ejection fraction
CO: blood volume pumped by the heart in 1 min (~5L/min)
SV: blood volume ejected by left ventricle in 1 contraction (70mL)
EF: fraction of blood volume in left ventricle ejected in 1 contraction (60%)
Effective Refractory period (ERP)
Time period after an action potential (or QRS complex) during which the heart is refractory to another action potential
SA node
- In the upper right atrium
- Highest level of automaticity; “sets the pace” for heart rate
AVN / AV node
- Between the atria & ventricles
- Slow conduction & behaves like an electrical filter during high atrial rates (e.g. atrial fibrillation
- Conduction here is mediated by L-type Ca current
Bundle of His & Bundle branches
Extends from distal end of the AV node & divides into smaller bundle branches in the ventricles, terminating in Purkinje fibers.
Specialized for rapid conduction of cardiac APs
Purkinje fibers
Specailized cardiac cells that spread out over the inner surface of the ventricles (endocardium).
Weakly contract, but are mostly specialized for rapid conduction of APs to the ventricular muscle.
The ___ is where the AP originates to stimulate heart contraction.
___ is specialized for slow conduction and prevents ventricles from being paced faster than they can fill with blood when atrial tachyarrhythmia occurs.
___ are specialized for rapid conduction & delives AP to the inner ventricular myocardium (nedocardium) via a web-like network of Purkinje fibers.
SA node- pace setter
AV node- slow conduction & prevents ventricles from pacing faster than they can fill during atrial tachyarrhythmia
His bundle- rapid conduction & delivery of APs to ventricles
Why do the ventricles have thicker walls (esp the left) than the atria?
They pump blood out of the heart into the rest of the body in systole
Steps of normal sinus rhythm
- Spontaneous apperance of APs in the SA node
- Spread of AP rapidly through the atria and into the AV node
- Slow conduction of AV node gives the atria time to contract and fill the ventricles
- AP reaches bundle of His, which divides into the left & right bundle branches on each side of the ventricular septum going toward the apex
- Divide into smaller Purkinje fibers that spread out all over the ventricular endocardium
- Conduction through HIs-Purkinje system is so fast that it basically simultaneously stimulates all muscle cells in both chambers
Intercalated discs between cardiac muscle fibers
Group of gap junctions between myocardial cells, allowing
- excitation to spread through cardiac muscle in the direction that muscle fibers are oriented.
- spread of metabolic or second msger signals btwn cells
Gap junctions of intercalated discs can “close” under conditions commonly produced during ____
myocardial ischemia
chronic depolarization of neighboring cells (depolarized resting potentials)
acidic conditions
high Cai
P wave
Atrial depolarization
PR interval
Delay in conduction that takes place in the AV node
QRS complex
Ventricular depolarization
Q wave: initial depolarization of septum before the ventricles
Things that widen the QRS complex (affects normal srpead of ventricular depolarization)
Na channel blocking drugs
Myocardial ischemia
Hyperkalemia
T wave
Ventricular repolarization
QT interval
time for complete ventricular repolarization
things that lengthen the QT interval
K-channel blocking drugs
Mutations in ion channels
long QT syndrome
Events that prolong the QT interval are typically proarrhythmic:
They increase the likelihood for multifocal ventricular arrhythmias such as Torsades de pointes –> life threatening
SAN, AVN, and Purkinje fibers all display
automaticity: ability to spontaneously depolarize an action potential
Demonstrated by the phase 4 depolarization
Action potentials in the SAN and AVN both have slow upstroke velocity caused by
L-type Ca current
The upstroke of APs in cells outside of the node
Na current
The 5 phases of a cardiac action potential
Why do different regions of the heart show differently shaped action potentials?
Cells in different regions express varying densities of the various ion channels that regulate the shape of the cardiac action potential
Ex) Atrial cells’ APs are much faster due to differences in ion channel expression
What ion channel is responsible for phase 4 when cardiac cells are left unstimulated?
The K-selective channel opens, producing an inwardly-rectifying K current called IK1
K ions leave the cell, but as they leave, other ions get stuck in the channel and block K+ efflux
What ion channel is responsibnle for phase 0?
Na channels transiently opening while K channels are closed
What maintains the plateau phase of the ventricular action potential (phase 2)?
Ito’s repolarizing effect is slowed by
- Activation of an L-type Ca current (ICa) causing Ca influx
- Inactivates slowly
- There’s a small (~1%) fraction of Na channels that don’t fully inactivate after depolarization
what is responsible for phase 1?
Ito: transient K efflux produces rapid repolarization
What’s responsible for the rapid repolarization of phase 3?
- Slow inactivation of the Ca current
- Activation of additional outward K currents (IKr & IKs)
The resting potential is a function of ____ concentration
extracellular K concentration
Hyperkalemia causes ______ of the resting potential
Depolarization
Hyperkalemia may result from
- Renal failure
- Addison’s disease (adrenal gland destruction)
- K-sparing diuretics
How does myocardial ischemia cause a depolarization of the resting potential?
Occlusion of a coronary artery will produce local tissue hyperkalemia
Relative refractory period (RRP)
time after the ERP during which conduction occurs, but at a less than maximal velocity bc not all Na channels have recovered from inactivation yet
Beats originating during the RRP have a slower upstroke velocity and produce a wider QRS complex
Avg resting heart is 70 bpm
Sympathetic nerves innervate the __; whereas, vagal nerves innervate the ___
Sympathetic innervates atria & ventricles
Vagal nerves innervate only the atria, SA node, AV node, and Purkinje fiber system
Depolarized resting potentials are common in cells exposed to severe stretch (opens non-selective ion channels) , hyperkalemia, or ischemia.
Depolarized resting potentials has what impact on the Na current?
Na channel inactivation
- Reduces Na current amplitude
- Slower action potentials (may even block conduction)
note: “rested”=available to be opened
Impact of neural stimulation on
- heart rate
- AV node ERP,
- PR
- contractility (SV)
note: vagal stimulation has little impact on contractility
Right vs left vagal nerve
Right affects SA
Left affects AV
Sympathetic stimulation: Norepinephrine binds to ____ receptors >__>__>__>___ phosphorylates the L-type Ca channel to allow Ca influx.
Parasympathetic: Acetylcholine binds to __ receptors >___> inhibits ___ & activates a ___
- SYMP: Norepi
- > Gs
- > adenylate cyclase
- > cAMP
- > PKA phosphorylates L-type Ca channel
- PARASYMP: Ach
- > type 2 muscarinic receptors
- > Gi
- > inhibits adenylate cyclase and activates a K channel resulting in K efflux (IKAch)
Why do cells at the nodes have a less negative diastolic membrane potential and slower upstroke velocity in phase 0 than atrial or ventricular cells?
Lower K+ permeability -> smaller IK1 -> less negative RP
Conduction is primarily Ca current-mediated -> slower upstroke velocity because the Ca current is much smaller than the Na current
How does Ach prolong the AV node ERP?
Increasing K conductance & Decreasing Ca conductance
–> AV node cell will have to wait more time for enough Ca channels to regain their excitability for conduction
Latent pacemakers
Ectopic pacemakers
Latent pacemaker: Cells outside the SAN that can become pacemakers
If SAN’s automaticity becomes depressed or cells outside the SAN become enhanced, then the region that starts generating APs outside the SAN is the ectopic pacemaker. AVN or Purkinje
bpm of san, avn, and purkinje
SAN = 70bpm (impacted by autonomics)
AVN= 40-60 bpm
Purkinje = 15-40 bpm
What is If?
funny, nonselective current that slowly activates upon hyperpolarization below a threshold of -50mV.
-> Na primarily enters ( depolarizing)
What are the sources of depolarizing current during diastole (phase 4) in the SAN & Purkinje fibers?
- SAN
- Both T- and L-type Ca currents
- If
-
Purkinje
- Just If
Ivabradine blocks If, thus __ the heart rate.
L-type Ca channel blockers will __ the heart rate due to their affect on ___.
Ivabradine reduces the heart rate
L-type Ca channel blockers also reduce HR thru their affect on the SAN (butalso by slowing conduction thru AV); can even cause bradycardia or asystole
Vagal stimulation vs Sympathetic stimulation on the slope of the phase 4 depolarization
Vagal stimulation -> greater K efflux in SAN & Purkinje –> less steep slope
Symp stimulation -> greater L-type Ca current & If -> steeper slope
How does hypokalemia result in development of an ectopic pacemaker activity?
Lowering [K]out causes EK and the maximum diastolic potential to be more negative.
-> Activates more If and reduces IKI
–> Enhances phase 4 depolarization in Purkinje (strong K permeability)
What Ca channels are the trigger for the SR to release its Ca into the cytoplasm?
What is the mechanism?
It’s the calcium from the L-type Ca channels participating in calcium-induced calcium release:
- Ca influx during AP plateau triggers the release of SR’s Ca into the cytoplasm.
- Large rise in free cytosolic Ca activates contraction of the myofilaments (systole).
- Relaxation (diastole) occurs following the
- reuptake of cytosolic Ca into the SR via SERCA
- extrusion of Ca into the extracellular fluid via Na/Ca exchange.
Excitation-Contraction Coupling
Infux of Ca from AP triggers release of Ca from the SR into the cytoplasm –> contraction
Reuptake of cytosolic Ca into the SR via SERCA and into the extracellular fluid via Na/Ca exchange –> relaxation
The more Ca released into the cytoplasm (e.g. B-adrenergic agonists), the increased
force of contraction
Contractility in cardiac tissue is sensitive both tot he amt of Ca influx, which regulates Ca-induced Ca released from the SR, as well as ___ because ___
intracellular & extracellular Na concentrations due to the role of the Na/Ca exchanger in clearing out the Ca afterwards
