Montemayor's DSA Flashcards
2 types of cardiac cells
contractile and autorhytmic
contractile cells
perform mechanical work (99%)
autorhythmic cells
initiate action potentials (1%)
atuomaticity
Self-stimulating: Heart’s ability to initiate its own beat Cyclic depolarization of autorhythmic cells initiates electrical activity independent of neural input
Order and timing of electrical events
a. SA node
b. Inter-atrial pathway
c. AV node
d. Common AV bundle (Bundle of His)
e. R & L Bundle branches
f. Purkinje fibers
functional syncytium
Myocytes can conduct APs cell-to-cell and thus contract as a single unit: due to gap junctions (electrical synapses)
average beats per minute for parts of conduction system
SA node- 60-100 bpm
Bundle of His- 40-60 bpm
purkinje fibers- 20-40 bpm
Sinoatrial Node
Normal pacemaker of the heart. Spontaneously depolarizing SA nodal cells: origin of normal electrical impulse.
Cells in right atrium: junction between SVC and RA
Interatrial tracts
atrial muscle conducts impulse radially from SA node through the RA. Internodal pathway (SA node--> AV node Anterior interatrial myocardial band (Bachmann's bundle): SA node --> left atrium.
Internodal pathway
anterior, middle, posterior
SA node–> AV node
Anterior interatrial myocardial band
Bachmann’s bundle
SA node –> left atrium
AV Node
Atrioventricular node: connects atria to ventricular conducting system
Located posteriorly on right side of interatrial septum (near ostium of the coronary sinus)
Bundle of His
Passes down right side of interventricular septum. Divides into R&L bundle branches
Right bundle branch
Direct continuation of bundle of His–> down right side of IV septum
Left bundle branch
Thicker than RBB, perforates IV septum.
Splits –> thin anterior division & thick posterior division
Purkinje fibers
Arise from RBB and Anterior & Posterior LBB
Complex network of conducting fibers spread out over subendocardial surfaces of R and L ventricles
Linearly arranged sarcomeres (like myocytes)
Typically lack T-tubule system
Largest diameter cardiac cells
Fastest conduction velocity in the heart
Rapid activation of Endocardium –> Epicardium, Apex –> Base
Pacemaker cells
SA node, AV node, Bundle of His and Purkinje fibers action potentials per minute: SA node- 70-80 AV node- 40-60 Bundle of His and Purkinje fibers- 20-40
what determines the pace?
autorhythmic cells which reach threshold first will drive the pace of the heart. If SA node is out, then AV node next at 40-60 bpm
What is the result of SA nodal failure?
bradycardia
how bradycardia results from SA node failure
SA nodal failure unmasks slower, latent pacemakers in the AV node or ventricular conduction system (escape beats or rhythms) → bradycardia
Example: Junctional rhythm (ectopic focus at the AV junction becomes pacemaker)
fastest conduction done by?
purkinje fibers (larger diamter –> decreased resistance). Bundle branches.
Slowest conduction by?
AV node: small diameter, increased resistance.
AV nodal delay: normal delay to allow time for optimal ventricular filling.
SA node
Ventricular myocytes
AV block or prolonged nodal delay may cause?
ventricular bradycardia
Result in distal pacemaker sites generating the ventricular rhythm
Secondary pacemaker sites have a lower intrinsic rate than the SA node
(e.g., Purkinje fibers ~ 20 – 40 bpm: very slow)
Normal order of ventricular depolarization
Step 1: AV node–> bundle branches
Step 2: IV septum depolarizes L–>R
Step 3: anteroseptal region depolarizes –> apex
Step 4: myocardium depolarizes from endocardium –> epicardium
Step 5: depolarization spreads from apex –> base via purkinje fibers
Step 6: ventricles are fully depolarized
repolarization occurs in the opposite order, and more slowly than depolarization phase
significance of order of events in ventricular depolarization
Early contraction of the IV septum:
Rigid anchor point for ventricular contraction
Early contraction of the papillary muscles:
Prevents prolapse of atrioventricular (AV) valves during ventricular systole
Final depolarization from apex to base:
Allows efficient emptying of ventricles into aorta and pulmonary trunk at the base
describe cardiac muscle
sarcomeres: z line to z line
striated- filaments (thick myosin and thin actin, troponin, tropomyosin)
mononucleated
intercalated disks: gap junctions (low resistance)
many mitochondria
t tubules & SR- calcium stores in ECF and SR
Calcium regulation of contraction: binds troponin
relatively slow speed of contraction
Biomarkers of myocardial injury
troponin (cTnT, cTnI)- commonly used iomarker for cardiac damage.
CK-MB- creatine kinase isoform specific to cardiac muscle.
Electrical syncytium of the heart
If one cardiac cell depolarizes, all will eventually depolarize via:
Gap junctions electrical connection (low resistance) allowing AP propagation cell-to-cell
Normally, cardiac APs are conducted via the conduction system to the ventricles and then spread cell-to-cell
Cell-to-cell conduction of APs is by ventricular myocytes is much slower than via Purkinje fibers
clinical correlate of ventricular depolarization that spreads only cell-to-cell via Gap Junctions:
slower than following the normal pathway of the conduction system. This slower process of spreading a depolarizing current through the ventricles results in the widening of the QRS complex on an ECG
Examples of arrhythmias where a widened QRS complex is commonly seen: Premature Ventricular Conductions (PVCs)
Ventricular Tachycardia
Atria and ventricles EACH form a functional syncytium–> contract as separate units
All-or-None Law for the Heart:
Normally, either all cardiac cells contract or none do
There is NO variation in force production via motor unit recruitment as in skeletal muscle
Due to functional syncytium
sources of calcium for cardiac contraction
Influx of extracellular Ca2+ is required for additional Ca2+ release from the SR (This is different from skeletal muscle)
2 Sources of Ca2+ in for Cardiac Contraction
Ca2+ influx from ECF via voltage-gated L-type Ca2+ channels (DHPR) during long plateau phase (phase 2) of cardiac m. AP
- Ca2+-induced (Ca2+-dependent) Ca2+ release from the SR via Ca2+- release channels (RYR)
Release of Ca2+ from the SR also required
Amount of Ca2+ from the ECF alone is too small to promote actin-myosin binding
Ca2+ influx from the ECF triggers Ca2+ release from the SR
Relaxation (diastole): removal of calcium by 3 pumps
Removal of Ca2+ to the ECF
1. 3Na+- 1Ca2+ antiporter [sarcolemma]
Ca2+ removal against large gradient
[Na+] higher in ECF, Na+ gradient powers Ca2+ removal
2. Ca2+ pump [sarcolemma]
ATP used to extrude Ca2+ from cell against gradient
Sequestering Ca2+ into the SR
3. SR Ca2+ pump (SERCA); Regulated by phospholamban
(β-adrenergic mediation of phosphorylation increases SERCA activity)
No Tetanus in Cardiac Muscle
Cardiac tetanus would be fatal because a sustained contraction would inhibit effective pumping of blood
Long AP in cardiac muscle results in a long refractory period
(Primarily due to L-type Ca2+ channels and slow, delayed K+ channel opening)
Thus, relaxation of myocytes occurs prior to complete repolarization of AP such that ‘twitches’ cannot be summed like they can in skeletal muscle
Resting membrane potential of cardiac cells
Pacemaker cells
No true RMP
“Maximum Diastolic Potential”
Spontaneous slow depolarization phase (phase 4)
Non-pacemaker cells
True resting potential (~ - 80 to - 90 mV) (phase 4)
Ion distribution
Membrane potential: Determined by ion concentration gradients and conductance (membrane permeability)
Time-dependent changes in membrane permeability and ion conductance result in depolarization and repolarization
Primary ions: Ca2+, K+ and Na+
K+ contribution to RMP
Resting cell membrane is relatively permeable to K+ (Much more permeable vs. Na+ and Ca2+)
Conductance to K+ (gK) is ~ 100x > conductance to Na+ (gNa)
Na+ contribution to the RMP
RMP: Because gNa is so small in the resting cell, changes in ECF [Na+] do not significantly affect resting membrane potential (Vm)
General properties of cardiac action potentials
Initiation time, shape, & duration of APs are distinct for cardiac cells of varied function within different cardiac regions
AP propagation requires careful timing to synchronize ventricular contraction to optimize ejection of blood
Main types of cardiac action potentials
Characterized by rate of depolarizing upstroke (phase 0)
1. Slow response:
SA & AV nodes
2. Fast response: Atrial, ventricular myocytes & Purkinje fibers
Fast response action potentials
Fast depolarizing upstroke (phase 0) Early, partial repolarization (phase 1) Plateau (phase 2) Final repolarization (phase 3) Resting potential (phase 4)
slow response action potentials
Slow depolarizing upstroke (phase 0)
Absent: early repolarization (phase 1)
Absent: Plateau is less prolonged or absent (phase 2)
Repolarization (phase 3)
No true resting potential (phase 4)
compare fast vs slow AP
Resting membrane potential (phase 4):
More negative in fast- response APs vs. slow response (no true)
Threshold potential:
Slow-response threshold potential: ~ −40 mV
Fast-response threshold potential: ~ −70 mV
Greater slope of upstroke (phase 0), AP amplitude, and extent of overshoot in fast-response vs. slow response
Conduction velocities:
Slow-response (SA & AV nodes)
major time-dependent & voltage-gated currents of cardiac APs
Na+ current (INa):
Primarily responsible for the rapid depolarizing phase in atrial m., ventricular m., and Purkinje fibers
Ca2+ current (ICa):
Responsible for the “rapid” depolarizing phase in SA node and AV node
Primarily responsible for plateau phase of fast-response APs
Triggers contraction in all contractile cardiomyocytes
K+ current (IK):
Responsible for the repolarizing phase in all cardiomyocytes
Pacemaker (“funny”) current (If):
Responsible, in part, for pacemaker activity (slow depolarization phase) in SA and AV nodal cells and sometimes Purkinje fibers
Funny channel = non-specific cation channel; primarily Na+ current
Phase O
Upstroke
Slow: if upstroke is only due to ICa
Fast: if upstroke is due to both INa and Ica
Phase 1
Early, rapid (partial) repolarization
Activation of minor K+ current (Ito = transient outward) Inactivation of INa or ICa (likely T-type Ca2+ channels)
Phase 2
Plateau phase
Continued influx of Ca2+ countered by small K+ current (Small, remaining Na+ current possible and a minor membrane current due to the Na-Ca exchanger)
Phase 3
Final Repolarization
IK in all cells
Phase 4
Electrical diastolic phase
Changes in IK, ICa, and If produce pacemaker activity in SA and AV nodal cells
Atrial and ventricular muscle have no time-dependent currents during phase 4
parts that use many voltage-gated sodium channels and a large Na current
ventricular m., atrial m., and purkinje fibers
Voltage-gated sodium channels
Closed at negative resting potentials
Rapidly activate when membrane depolarizes to threshold
Na+ influx mainly responsible for rapid upstroke of AP (phase 0)
Inactivation gates close when membrane depolarizes
Partial role in the early repolarization of the AP (phase 1)
Within the range of positive voltages, a very small INa remains: prolongs plateau phase (phase 2)
Magnitude of INa: impacts regenerative conduction of APs
Sodium at the SA and AV nodes
If = “funny” or “pacemaker” current
Activated on hyperpolarization
Non-specific channel: ↑ Na+ and K+ currents
Increased Na+ influx is primarily responsible for initiation of slow depolarization phase (phase 4)
Calcium
ICa: all cardiac myocytes
Majority: L-type Ca2+ channel (Long-lived, DHPR)
Fewer T-type Ca2+ channels (Transient)
Calcium at SA and AV nodes
ICa contributes to pacemaker activity (phase 4)
ICa (influx) contributes to upstroke (phase 0)
ICa is smaller than INa
Nodal cells: slower upstroke vs. atrial & ventricular m.m.
APs in nodal cells: slower conduction velocity because the smaller ICa depolarizes adjacent cells more slowly
Calcium at the Ventricular m. Atrial m. and purkinje fibers
Smaller ICa adds to INa during the upstroke (phase 0)
Ca2+ channels are closed at negative RMP
Activate at more positive voltages (near upstroke peak, ∼1 ms) Inactivate (slower than Na+ channels, ~ 10 to 20 ms, time-dependent)
Small ICa prolongs plateau (phase 2) 1° via L-type Ca2+ channels
Ca2+ entering through L-type Ca2+ channels activates release of Ca2+ from SR via calcium-induced Ca2+ release in atrial & ventricular m.m.
Potassium
All cardiac myocytes:
Slow, delayed IK also contributes, in part, to relatively long cardiac APs
IK: contributes to repolarization in all cardiac myocytes (phase 3)
2 major IK contribute to repolarization (there are other K+ currents):
IKR : relatively rapid
IKS : relatively slow
IK: very small at negative voltages
Slowly activates with depolarization (~ 20 to 100 ms), does not inactivate
Potassium at SA and AV node
IK decreases at the end of phase 4, contributing to pacemaker activity (decreasing K+ efflux promotes depolarization)
