Electrophysiology of the Heart Flashcards
Lecture 18
What is coupled with heart muscle contraction?
generation of action potentials in cells
What are the 2 main types of cells of the heart?
Conducting cells and contractile cells
Where are conducting cells found?
In SA/AV nodes, atrial internodal tracts, Bundle of His, Purkinje system.
2 properties of all cardiac cells
automaticity (generate own AP) and rhythmicity (generate APs in regular, repetitive manner
Gap junctions between cardiomyocytes
Allow the heart to behave as one big cell; cells are coupled electrically through gap junctions
What voltage-gated channels open when an AP occurs?
Sodium, calcium, and potassium
SA node
source of initial electrical impulse
pacemaker (60-100 AP/min)
Overdrive suppression
The SA node’s ability to keep other conducting cells from spontaneously firing
Where does the AP of the SA node spread to cause the atria to contract?
internodal/interarterial fibers
P wave in EKG
depolarization of the atria
What blocks from electrical impulse flow from the SA nodes into the ventricles?
Annulus fibrosus
-E.I. can only get into ventricles through the AV node
What is the result of the small lag time between the conduction of the AP from the atrium to the ventricles due to the only point of conduction being the AV node to the ventricles?
Maximum atrial contraction helps fill the ventricles to the maximum; AV node conduction is slowest which helps the ventricles fill
Pathway of action potential conduction from AV node
SA node–> AV node–> Bundle of His–> Purkinje fibers
this correlates with the QRS complex in the EKG
QRS complex
AV node–> Bundle of His–> Purkinje fibers
T wave
ventricular repolarization
Slowest conduction velocities
AV node
Fastest conduction velocities
Purkinje fibers
Order of conduction velocities
SA/AV node < Atrial pathway/Ventricular cardiomyocytes < Purkinje fibers
What does an EKG record?
Electrical extracellular signals produced by AP in cardiac myocytes.
P wave
-sequential depolarization of R/L atria and atrial muscle action potential
What things are not seen on an EKG?
SA node depolarization/repolarization, AV node depolarization/repolarization
QRS complex
R/L ventricular depolarization/AP
ST wave
isoelectric, plateau of ventricular AP to rapid ejection phase; myocardium maintain contraction to expel blood
QT interval
duration of ventricular depolarization and repolarization
QT interval is inversely proportional to what?
HR; can be altered by drugs that alter repolarization
What happens if ventricular repolarization is delayed?
QT interval is prolonged
What health issue is delayed ventricular repolarization associated with?
Ventricular arrhythmias
Delayed repolarization results in?
Ventricular arrhythmias
Slow AP response
SA/AV nodes
Fast AP response
normal atrium/ventricular cardiomyocytes and Purkinje fibers
Phase 0 FR
fast upstroke
voltage-gated Na+ channels open
influx of Na+ into cell
Phase 1 FR
partial repolarization
inactivation of Na+ channels
rapid opening/closing of K+
K+ leaves the cell
Phase 2 FR
plateau phase
voltage-sensitive Ca2+ channels open, influx of Ca2+
counterbalanced by slow efflux of K+ through VG-K+ channels
What is unique about voltage-gated Ca2+ channels?
slower opening/closing kinetics
Phase 3 FR
repolarization inactivation of Ca2+ channels efflux of K+ via VG channels repolarization of cell membrane Na/K ATPase corrects Na/K levels
Phase 4 FR
cardiomyocytes at rest, resting membrane potential
background Na+ influx and K+ efflux through leak K+ channels
What comes before Phase 0 FR?
suprathreshold stimulus from a pacemaker cell
resting membrane potential is abruptly changed
Activation gate of Na+ channel
closed at resting membrane potential, opens with depolarization
Inactivation gate of Na+ channel
open at rest, closed during depolarization
During what phases are Ca2+ channels open?
Phase 0 and 2
What is the contribution of Ca2+ during phase 0?
It makes the AP upstroke steeper and velocity faster
AP leads to Calcium influx, which in turn causes…
cardiac muscle contraction
Steps of Ca release
Depolarization–> Ca2+ channels open–> influx of Ca2+–> Ca2+ binds troponin C–> troponin C interacts with tropomyosin–> exposed actin/myosin binding sites–> cross-bridge cycling–> CONTRACTION
Where does the Ca2+ come from that interacts with troponin C?
It comes from the sarcoplasmic reticulum
extracellular calcium is used for Calcium-induced Calcium release
What enhances myocardial contraction?
catecholamines bind B-adrenergic receptors
inhibiting Na/K ATPase
B-adrenergic activation
increased Ca2+ influx of L-type VG-Ca2+ channels
Inhibition of Na/K/ATPase
increased Na+ leads to the decrease of the Na/Ca transporter, more calcium in the cell
Plateau phase
as long as K+ efflux is balanced by Ca2+ influx
What happens if K+ efflux exceeds Ca2+ influx during Phase 2?
plateau duration is short and final repolarization happens early
Effective refractory period
cell will not respond to any stimuli
Relative refractory period
some Na+ channels are excitable and can generate a smaller AP
Diastolic depolarization
decreasing K+ efflux because VGK+ channels are inactivated–> increasing Na+ influx through HCN; results in further depolarization–> Calcium release from SR–> increase in Ca2+ leads to increase NCX–> at -50 mV, Ltype Ca2+ channels open–> increased Ca2+ influx leads to CICR–> K+ VG channels open, repolarization–> SR refills with Ca2+
Differences in fast/slow response
Slow response has:
- unstable phase 4
- slower upstroke in phase 0
- no phase 1 or 2 (no early repolarization/plateau)
Sympathetic nervous system effect on HR
increased HR
SNS pathway to increased HR
- Norepinephrine/epinephrine binds B1 adrenergic receptors in SA/AV nodal cells
- Adenylyl cyclase activated
- increased cAMP
- cAMP phosphorylates protein kinase
- PK phosphorylates HCN/VG-Ca2+ channels
- leads to increased Na influx through HCN/increased Ca2+ influx through VG-Ca2+ channels
- steepens phase 4 of pacemaker potential
Parasympathetic nervous system effect on HR
decreased HR
PNS pathway to reduced HR
- acetylcholine binds M2 cholinergic receptors
- inhibits adenylyl cyclase
- less cAMP
- less Na+ influx through HCN/less Ca2+ influx through VG-Ca2+ channels
- reduces steepness of phase 4
2 types of effects of SNS activation of B1-adrenergic receptors?
Inotropic effect
Lusitropic effect
Inotropic effect
increased cardiac contractility
increase Ca2+ influx= increase CICR
Lusitrophic effect
faster atrial/ventricular relaxation
cAMP/PKA phosphorylate phospholamban which increases SRCa2+ ATPase, which pumps Ca2+ back into SR.
Ca2+ removed more quickly
What does PKA do to Troponin during Lusitropic effect?
It phosphorylates Troponin I, destabilizing actin-myosin cross-bridging
