Action Potential,Resting Membrane Potential and Conduction System (Montemayor) Flashcards
what are the types cardiac cells
contractile cells - perform mechanical work
autorhythmic cells- initiate action potentials
automaticity of the heart?
self stimulating AP
cyclic depolarization of autorhythmic cells independent of neural input
Specialized cells in atria & ventricles initiate electrical activity required for mechanical contraction (heartbeat)
Located mainly in nodal tissues or specialized conducting fibers [Conduction System]
what is the order and timing of electrical events in the heart.
SA node inter-atrial pathway AV node Common AV bundle (bundle of his) R and L bundle branches Purkinje fibers
what is the functional syncytium
myocytes contract as a single unit due to gap junctions
what is the location and function of the SA node
right atrial wall just inferior to opening of superior vena cava
primary PACEMAKER (80-100 bpm) rate of reaching threshold is fastest and drives the heart rate
initiates impulse that is normally conducted throughout the left and right atria
what is the location and function of the AV node
floor of the right atrium immediately behind the tricuspid valve and near the opening of the coronary sinus
***connects atira to ventricular conducting system
receive impulse from the SA node and delays relay of the impulse to the bundle of HIs allowing time for the atria to empty their contents into the ventricles before the onset of ventricular contraction
40-60 bpm
location function of bundle of his
Superior portion of interventricular septum
receives impulse from AV node and relays it to right and left bundle branches
where is the location and what is the function of right and left bundle branches
interventricular septum
receives impulse from bundle of His and relays it to Purkinje fibers
RBB–> direct continuation of bundle of His—> down right side of IV septum
LBB–> thicker than RBB, perforates IV septum
splits–> thin anterior division and thick posterior division
function and location of Purkinje fibers
arise from RBB and Anterior and Posterior LBB
spread out over subendocardial surfaces of R and L ventricles
receives impulse from bundle branches and relays it to ventricular myocardium
FASTEST CONDUCTION VELOCITY and largest diameter cardiac cells (increase diameter and decrease internal resistance)
30-40 bpm
rapid activation of endocardium layer–> epicardium layer and then –> Apex–> base
what is the cause of bradycardia
SA nodal failure
this leads to unmasking of slower, latent pacemakers in the AV node or ventricular conduction system
how does the SA node get the impulse to the right atrium?
internodal pathway (anterior, middle and posterior)
how does the SA node get the impulse to the left atrium
anterior interatrial myocardial band (Bachmann’s bundle)
what is the AV junction and what are the regions
AN region-transitional zone between atrium and the node ***
N region- midportion of the AV node
NH region- nodal fibers merge with bundle of his
why is there a delay between atrial and ventricular excitation? AV nodal delay
so there is time for filling !
adequate filling time during diastole of the ventricles
how does the AV nodal delay occur
because the AN region has a longer conduction path
the N region has a slower conduction velocity
how does the heart prevent atrial fibrillation or flutter
decremental conduction
increase in stimulation frequency actually causes a decrease in conduction velocity
this limits the rate of conduction to the ventricles from accelerated atrial rhythms
what can lead to Ventricular bradycardia
AV block- so the AV node is essentially knocked out
results in distal pacemaker sites generating the ventricular rhythm –> secondary pacemaker sites have a lower intrinsic rate than the SA node
purkinje fibers –> 20-40 bpm (slow)
what is Wolff Parkinson white syndrome
**May result in reentry and is a cause of supraventricular (above ventricles) tachyarrythmias **
Alternate path around AV node (Bundle of Kent)
(accessory conduction pathway)
AP conducted directly: atria –> ventricle
Faster than normal AV nodal pathway
Ventricular depolarization is generally slower than normal
Accessory depolarization path does not follow normal path of purkinje fibers
what are the steps in AP conduction (location wise)
AV node –> bundle branches
IV septum depolarized L–> R
Anteroseptal region depolarizes
myocardium depolarizes from endocardium –> epicardium
depolarization spreads from apex –> base via Purkinje fibers
ventricles are fully depolarized
why is there early contraction of the IV septum
rigid: anchor point for ventricular contraction
why is there early contraction of the papillary muscles
prevents prolapse of atrioventricular valves during ventricular systole
why is there depolarization from apex to base
allows efficient emptying of ventricles into aorta and pulmonary trunk at the base
what are the fastest conductors of the conduction system of the heart?
purkinje fibers (due to larger diameter and lower internal resistance)
bundle branches
what are the slowest conductors of the conduction system of the heart?
AV node
SA node
small diameter–> increased resistance
where does cardiac muscle store calcium
ECF and SR
what is characteristic of cardiac muscle
striated
mononucleated
intercalated disks (gap junctions (low resistance))
T-tubules and SR (Ca stores in ECF and SR)***
Ca 2+ regulation of contraction: binds troponin
Relatively slow speed of contraction***
Biomarkers of myocardial injury?
Troponin (cTnT, cTnl)
CK -MB
what is the functional sycytium
Cardiac
cells contract in synchrony
what are intercalated disks
connect cardiac cells through mechanical junctions and electrical connections
desmosomes- mechanical, so cell doesn’t pull apart when it contracts
Gap junctions -electrical connection (low resistance) allowing AP propagation
what is one way a widening of the QRS complex can happen (in terms of the functional syncytium)
Ventricular depolarization that spreads only cell to cell via gap junctions results in the widening of the QRS complex (PVC’s, Ventricular Tachycardia)
group of cells firing in their own rate, taking longer than normally would see
do the atria and ventricles contract as separate units?
YES
each form a functional syncytium
what is the all or non law for the heart and how is this different than skeletal muscle?
all cardiac cells contract or NONE do
no variation in force production via motor unit recruitment (as can be done in skeletal muscle)
this is due to the functional syncytium and conduction system
what is contractility in terms of the heart
increased force contraction is modified by altering sympathetic NS input (increasing Ca2+ permeability)
so it is INDEPENDENT of initial fiber length or preload
what is the role of extracellular Ca in cardiac contraction
influx of extracellular Ca is REQUIRED for additional Ca release from the SR
Release of Ca2+ from SR is also required
this is called Ca induced (Ca dependent) Ca release from the SR through Ca release channels RYR (ryanodine receptors)
amount of Ca from ECF alone is too small to promote actin-myosin binding
Ca influx from ECF triggers Ca release from SR
Ca release channels remain open longer
what channels does Ca use to get in from the ECF
from ECF via voltage gated L type Ca channels during long plateau phase of cardiac muscle AP
how does relaxation of cardiac muscle occur
3 things
Removal of Ca to the ECF
- 3Na-1Ca antiporter
- Sarcolemmal Ca2 pump
Sequestering Ca into the SR
SERCA
how does the Sarcolemmal 3Na 1Ca antiporter work
moves ca against large gradient
na higher in the ECF, so uses the Na gradient to power Ca2+ removal
*** if the Na concentration in the ECF is abnormal this pump might not work properly
how does the sarcolemmal Ca2 pump work
uses ATP to extrude Ca from cell against gradient
How does the SERCA pump work
Ca back in the SR
regulated by phospholamban
b-adrenergic mediation of phosphorylation increases SERCA activity
is there tetanus in cardiac muscle
and what pumps are contributing to the cardiac muscle either having or not having tetanus
NO (unlike skeletal muscle)
cardiac muscle cannot increase force of contraction through tetanus
AP is so long, can’t sum twitches, long refractory period
GOOD b/c tetanus would be fatal because effective pumping would be inhibited
**Primarily due to activation of voltage gated L type Ca channels and slow delayed K channel opening **
what is the difference between the pacemaker cells and non pacemaker cells in terms of resting membrane potential
pacemaker cells have no resting potential -just have a maximum diastolic potential (spontaneous slow depolarization phase)
nonpacemaker cells have a true resting potential (-80 to -90mV)
which ions have the greatest impact on resting membrane potential and describe the primary distribution
K- high inside
Ca- very high outside compared with inside
Na- very high outside compared with inside
what is the K+ contribution to the RMP
resting cell membrane is relatively permeable to K+ (much more than Na and Ca)
LEAK CHANNELS
hyperkalemia –> depolarize the membrane
what is the Na contribution to the RMP
Because gNa is so small in the resting cell, changes in ECF (na) do not significantly affect Vm
what is the main contributor to the peak value of the upstroke of the AP (of non-pacemaker cells
Na
change in the ECF concentration of Na can change the amplitude of the AP
why does AP propagation require careful timing?
to synchronize ventricular contraction to optimize ejection of blood
initiation time, shape and duration of AP’s are distinct for cells of varied function within cardiac regions
APs characterized by slow rate of depolarizing upstroke …
SA and AV nodes
AP’s characterized by fast rate of depolarizing upstroke
Atrial myocytes, purkinje fibers and ventricular myocytes
2 main types of cardiac action potentials
fast
- higher amplitude
- faster conduction velocity
slow (sa nodes and av nodes)
- no true resting membrane potential
- maximum diastolic potential is less negative than starting point of the fast response
- lesser amplitude
fast vs slow resting membrane potential
more negative in fast
fast vs slow threshold potential
slow - reach threshold at -40
fast - reach threshold at about -70 mV
what contributes to how fast an AP is propagated
2 things
AP amplitude and upstroke slope
in which AP (slow or Fast) tissue type is conduction block more likely to happen
in slow response tissue b/c it is slower
what are the 4 major time dependent and voltage gated currents
Na
-rapid depolarizing phase in atrial, ventricular, and Purkinje fibers
Ca
-“rapid” depolarizing phase in the SA node and AV node
primarily responsible for plateau phase of fast-response AP’s
Triggers contraction in all contractile cardiomyocytes
K
-repolarizing phase in all cardiomyocytes
Pacemaker funny current
-pacemaker activity (slow depolarization phase) in SA and AV nodal cells and sometimes Purkinje fibers
what is going on at phase 0 for slow and fast
UPSTROKE
slow
due to Ca current inward
fast
due to both Na and little bit of Ca influx
what is going on at phase 1
early rapid partial repolarization
only associated with fast responses
activation of minor K+ current (transient)
inactivation of Ina and Ica (likely T-type Ca 2+ channels)
what is going on in the 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)
what is going on in phase 3
FINAL repolarization
depends on K current in cells (so K efflux)
what is going on in phase 4
electrical diastolic phase
changes in K Ca and funny current produce pacemaker activity in SA and AV nodal cells
Atrial and ventricular muscle have no time-dependent currents during phase 4 (this is when there is no inward or outward flux of K, Na or Ca)
Na + role
Ventricular m., atrial m., and Purkinje fibers have many voltage-gated Na+ channels and a large Na+ current (INa)
closed at negative resting potentials and rapidly activate when membrane depolarizes to threshold
Na influx mainly responsible for rapid upstroke of AP (phase 0)
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)
what does the magnitude of the Na current impact?
impacts regenerative conduction of AP’s
depolarization induced by na current activates both na current in adjacent cells and other currents in the same cell (Ca and K)
what are L-type Ca channels
long -lived
what are the T-type Ca channels
transient
what is the role of Ca2+ in slow type tissue
SA nodes and AV nodes
contributes to pacemaker activity (gradual ) phase 4
influx contributes to upstroke (phase 0) (major contribution)
Ca is smaller than Na current
-this is obvious with the slower upstroke of Nodal cells versus atrial and ventricular mm.
why are AP’s in nodal cells smaller?
slower conduction velocity because the smaller ca current depolarizes adjacent cells more slowly
what is the role of Ca in fast type tissue
ventricular, atrial and purkinje fibers
smaller Ca influx during phase O but larger contribution from Na
activated more slowly than voltage gated sodium channels (b/c they have more positive voltage they need to be activate dat) and close more slowly
what is the major contributor to the prolonged plateau phase in fast type tissue
L-type Ca channels
Ca entering through L type Ca channels activates the release of Ca from the SR by calcium-induced Ca release in atrial and ventricular mm
what is potassiums role
the slow, delayed current of K contributes to the relatively long cardiac Ap’s
the K current is responsible for repolarization at the end of the ap in both fast and slow types (phase 3)
slowly activates with depolarization and does not inactivate
what is happening with the K current at negative diastolic voltage in SA and AV nodes
K current decreases at this voltage contributing to the pacemaker activity
decreasing K+ efflux promotes depolarization
what happens in phase 0 of fast type
upstroke, spike, overshoot
beings with depolarization opens voltage gated Na channels –> rapid Na influx, minor contributor is slower Ca influx and K efflux
inactivation gates kick in more slowly as it passes threshold
also note ECF Na affects AP amplitude
what happens with hypernatremia?
it affects the maximum upstroke
with increase in ECF na there is a larger AP amplitude (the peak of the AP increases )
what happens in phase 1 of fast type
early repolarization
primarily due to K efflux via K(transient) channels
Na influx SLOWS as majority of Na channels inactivate
Delayed Ca influx (plateau) phase begins
what happens with 4-aminopyridine (K+channel blocker)
the notch in phase 1 is less prominent b/c there is probably not as much K+ efflux
what happens in phase 2 of fast type ?
primarily due to slow Ca2 influx (L-type)
slow efflux continues
contributes to longer duration of Cardiac AP **
what happens in phase 3 of fast type
rapid repolarization due to K efflux
na and ca channels are CLOSED
what happens if K+ channels are blocked
the AP duration will increase
delayed repolarization
what happens in phase 4 of fast type
resting membrane potential
fully polarized state of resting cardiac cell
membrane will remain polarized until reactivated by another stimulus
what is unique about the atrial muscle AP
has 3 time/voltage dependent currents (na k ca)
AP duration SHORTNER in ATRIAL vs. ventricular: due to greater efflux of K+ during plateau phase ***
no pacemaker activity
what is unique about Ventricular muscle AP
3 time/voltage dependent currents (na k ca)
no pacemaker activity
rapid upstroke
plateau phase is prolonged (ca current activates SR ca release for contraction)
AP duration varies among ventricular cells: differences in the delayed rectifier K+ current
what is conduction velocity
how quickly an AP can be conducted to an adjacent cell
what does conduction velocity depend on
Amplitude of the AP
-greater amplitude can more effectively depolarize adjacent membrane
Rate of change of potential during phase 0
- slope of depolarization
- if depolarization is too gradual it may not produce depolarization in adjacent membrane
what two things CAN impact AP amplitude
RMP (Vm) and Na (ECF) outside cell
Normal AP: depolarization is so fast inactivation gates do not tend to close until end of phase 0 BUT
If a partial depolarization of RMP occurs gradually, inactivation gates have time to close
If many Na+ channels are already inactivated, only a fraction are open for Na+ influx during phase 0
Decreases amplitude & slope of depolarization –> slows conduction velocity
what is the problem with hyperkalemia
SLOWS CONDUCTION VELOCITY
may cause cell to be in a persistent slightly depolarized state and this can cause Na channels to be in inactivation state. so the amount of Na channels available for sodium influx to respond to an AP will be LESS therefore smaller influx of Na and lower slope of phase 0 and a lower amplitude –> decrease conduction velocity
at high enough K ECF Vm is depolarized to inactivate majority of fast Na channels and the fast-response AP’s begin to look like slow -response AP’s
what happens with blood flow reduction and ischemia of heart (Coronary artery disease)
decrease metabolic substrates powering Na+/K+-ATPase (the NaK pump)
Impairment: Excess intracellular Na+ and excess extracellular K+
Elevated [K+]o can result in rhythm disruption
what happens with MI in terms of ECF K concentration
Infarcted cells release intracellular K+ stores causing increase in ECF K
what is the effective (absolute) refractory period
After initiation of fast response AP, the depolarized cell is no longer excitable until the cell is partially repolarized
Time during which a subsequent electrical stimulus (of any size) has no effect
from phase 0 to mid phase 3
***it is due to the fact that Na and Ca are largely inactivated by depolarization (inactivation gates)
what is the relative refractory period
fiber is not fully excitable until complete repolarization
Before repolarization is complete, another AP may be initiated if stimulus is strong enough
ICa, INa: inactivation gates open with repolarization
Phase 3: repolarization with increased IK (efflux)
what are the various outcomes with initiation of AP during relative refractory period at different times?
AP characteristics vary based on Vm at time of stimulation
The later in the relative refractory period the greater the amplitude and slope of upstroke (greater the conduction velocity)
this is because there are more fast Na channels recovered from inactivation as repolarization proceeds during phase 3
why is the refractory period important in cardiac muscle
It prevents sustained tetanic contraction
- Relaxation of cardiac muscle: mainly during AP phase 4
- Tetanus would result in sustained contraction & interfere with normal intermittent contractions that promote effective pumping (adequate filling)
Safety measure
-limits extraneous pacemakers from triggering ectopic (out of place) beats which would reduce pump efficiency
what is ectopic foci and what does it cause
generate AP’s that do not follow normal conduction pathway
myocytes take longer to depolarize cell-to-cell via gap junctions
cause premature contractions
what does a ventricular ectopic foci look like on EKG
wide QRS
what are the possible causes of ectopic foci
Local areas of ischemia
Mildly toxic conditions can irritate fibers of the A-V node, Purkinje system, or myocardium (ex: various drugs, nicotine, or caffeine, alcohol)
Calcified plaques irritating adjacent cardiac fibers
Cardiac catheterization: mechanical initiation of premature contractions
what are afterdepolarizations
Abnormal depolarizations of cardiac myocytes that interrupt phase (2), 3, or 4 of the AP
the earlier the more detrimental
what can afterdepolarizations cause?
tachycardia
May increase pacemaker activity of existing pacemakers, induce pacemaker activity in Purkinje fibers, or in ventricular myocytes
May trigger extra systole (PVC)
Series of extra systoles (3+) –> ventricular tachycardia (can lead to ventricular fibrillation
can set up an oscillatory repolarization
what happens with an Early Afterdepolarization (EAD)
Increased frequency of abortive APs
Abnormal depolarization late phase 2 or phase 3
Phase 2 interruption: augmented Ca2+ channel opening
Phase 3 interruption: Na+ channels open or delayed inactivation
Ex: Long QT Syndrome –> Torsades de Pointes
what happens with delayed afterdepolarizations (DAD)
Ap generation during phase 4 depolarization before another AP would normally occur
elevated Ca2+ (digoxin toxicity)
how does the timing of premature depolarization determine clinical consequence?
late in RRP or after full repolarization–> little consequence
early in RRP likely slowed conduction of the early impulse
REENTRY is more likely to occur
fibrillation may develop –> inefficient contractions can lead to death
what is reentry
abnormal impulse conduction may re-excite myocardial regions through which an impulse has already passed
CIRCUS movements
responsible for many arrhythmias –> fibrillation
requires UNIDIRECTIONAL BLOCK
need at whatever location, need the region where the signal reenters in the improper way to enter in area where it is out of the refractory period
what is global reentry
Macro reentry
between atria and ventricles BACKWARDS
can cause Supraventricular tachycardia (SVT)
Wolff-Parkinson-White syndrome
what is local reentry
Microreentry
within the atria or ventricles
cause atrial or ventricular tachycardia
Requirements for Reentry
Partial depolarizaiton of a conduction pathway
unidirectional block
timing: reentrant current must occur beyond ERP
how can alterations in autonomic input promote or block reentry
if you have sympathetic activation of AV node and ventricular conduction pathways then you increase conduction velocity and decrease ERP
if you have vagal activation of AV node you decrease conduction velocity and increase ERP
3 factors promoting reentry in pathological cardiac conditions ***
lengthened conduction pathway
- commonly occurs in dilated heart chambers
- atrial fibrillation due to atrial enlargemnet associated with valve lesions or ventricular failure
decreased conduction velocity (slope and amplitude)
-Purkinje system block, ischemia, hyperkalemia
reduced refractory period
- can occur in response to various drugs
- epinephrine
what is the result of circus movements?
fibrillation
what does an external automated defibrillator do
strong high voltage alternating current can promote a “re-set” by putting all cells into refractoriness at once STOPPING fibrillation
what are some characteristics of Slow response AP’s that is different from Fast-response
and what is the key one??
No true RMP
-Slow depolarization (pacemaker potential)** KEY
Less steep AP upstroke (phase 0)
-Minimal INa contribution
No early repolarization (phase 1)
Absent or less distinct plateau (phase 2)
Gradual repolarization (phase 3)
Less negative Vm during “rest” (~ − 60/65 mV) (phase 4)
Less IK, less negative Vm (retain intracellular +); funny current mainly Na+ influx
firing frequency of pacemaker cells can be altered how?? 3 things
Depolarization rate (altering ion currents)
Vm during phase 4 (starting point)
threshold
what is in charge/responsible for the slow diastolic depolarization (phase 4) in slow response AP’s
Funny current (non-specific cation channel) -inward (mainly Na) activated during HYPERpolarization
increase Ca influx
decrease K efflux
what is the funny current
opens at progressively more negative voltages
slow activation near end of depolarization (phase 3)
activated when Vm reaches -50 mV (as repolarizing)
***activation increases with increasingly negative Vm
mainly Na influx
what is the role of calcium current in slow AP response
contributes to slow diastolic depolarization
activate near end of phase 4
influx of Ca increases rate of depolarization to threshold
MAJOR CONTRIBUTOR to AP upstroke (phase 0)
what would happen to slow response Ap’s if ECF Ca is changed
Increase–> increase amplitude and upstroke
Decrease –> exact opposite
what is the role of K is the slow AP response
major current contributing to REPOLARIZATION
K current opposes Funny and Ca currents during phase 4
K efflux gradually decreases during phase 4 which helps DECREASE the opposition to ca and funny currents allowing threshold to be reached again
How does hyperkalemia affect heart rate
increase in ECF K –> leads to decrease in HR
changes in driving force for K efflux
slows phase 4 depolarization
increases AP duration in nodal cells
delay in reaching hyperpolarization voltage required to activate funny current that is needed to start the slow depolarization
what effect does an AP evoked in the RRP have in slow response refractory periods?
how is the recovery time to full excitability in slow response compared to fast response AP’s
AP evoked EARLY have small amplitudes and shallow upstrokes
***Results in slower conduction velocity and can lead to conduction blocks
AP evoked later have progressively increasing amplitudes and upstroke slopes
**Recovery of full excitability is slower than in fast response AP’s
which pacemaker rate is faster. SA or AV
SA
so if SA node fails, AV node can take over pacemaker role to drive HR
and if both SA and AV nodes fail than purkinje fibers take over
what does tetrodotoxin do?
blocks fast Na channels –> fast response fiber can generate slow response
Purkinje fibers can exhibit both fast-response and slow response AP’s
what do purkinje fibers do?
have 4 time/voltage dependent currents
typically exhibit fast response AP’s and rapidly conduct AP’s due mainly to I na
slowest intrinsic pacemaker rate
