11. Basic EKG Flashcards
Responsible for the rapid upstroke (phase 0) of AP in non pacemaker cells
Na entry through fast Na channesl
Responsible for depolarization of pacemaker cells (PKJ and myocytes) or phase 2
Ca entry through Ca channels
Responsible for repolarization leading to resting potential or Phase 4 of nonpacemaker cells
K+ EXIT through K+ channel
What maintains the low intracell Ca++ concentration
Na/Ca exchanger
What maintains conc gradients for Ca/K/Na
Na/KATPase pump
How is Ca removed to external environment and to SR
via active Ca transporters.
Channel responsible for rapid depolarizing non-nodal
INa+
Channel that depolarizes nodal AP and myocyte contraction
ICa+
Channel responsible for repolarizing all myocytes
IK+ (activated during repolarization)
Channel that is key for pacemaker current and activated during hyperpolarization
If or the funny channel = Na/K channel
What is the basic structure of ion channels
glycosylated proteins with repeat transmembrane domains. Each domain has 6 segments
Difference between Na, K, Ca channels
K: has 4 seperate domains in tetramer Ca and Na have 4 domains covalently linked as single uint
What part of Na channel serves as inactivation gate?
part connecting domains III and IV
What part of Na channel has sequence of + charged aas?
S4 segment of each domain==confers channels voltage sensitivity
What forms the selective filter in the Na channel?
Segment 5 and 6 of peptide loops allow only Na in
What is the confirmation of the inactive and active gates in the “Resting” state of Na channel
The inactivation gate is open but the activation gate is closed thus Na+ ions cannot get back in
How do we open up the activation gate in the ‘resting’ state of the Na channel?
Rapid depolarization changes cell membrane voltage– forces the activation gate to open (remember inactivation gate is already open) Na++ can then permeate the cell
How does the Na+ channel close or transition to the “inactive” state
Inactivation gate will spontaneously and quickly close via the peptide loop between III and IV then Na+ current ceases.
Channel can’t reopen directly from the inactive state–How do we get back to the “resting” state
Cellular repolarization returns channel to resting condition… at high negative membrane voltages, the acitvation gate closes and the inactivation gate reopens
Resting potential of cardiac cell is determined by balance of concentration gradient and electrostatic forces of:
Potassium. K+ is the only channel open at rest!
Concentration gradient favors____ movement while electrostatic favors ______ movement
outward inward
How do we approximate the resting membrane potential?
Nernst for K+ -26.7ln ([K+]in/[K+]out) = -91mV
What is the equilibrium potential for Na Ca K
Na: +70 mV Ca: +130 mV K: -90 mV
Label the following as having greater intracellular or extracellular concentrations Na: Ca: K:
Na: greater extracellular Ca: greater extracellular K: greater intracellular
Whats going on in Phase 4?
This is our resting potential
What stage is depolarization and what is happening
Phase 0… have influx of Na+ and get a rapid upstroke
What is resonsible for partial repolarization during phase 1
Transient outward K+ current gives partial repolarization
What causes the platue in phase 2?
slow Ca++ influx
What’s responsible for the rapid repolarization in phase 3?
Rapid efflux of K+
Largest current in the heart
Has classic voltage gated channel with a and b subunits
Na+
What subunits in Na+ gated channel can be phosphorylated by cAMP dependent kinase (PKA)
subunit a
Some Na channels stay activated during platue phase which will:
prolounge phase 2
How is depolarization spread through neighboring cells?
Major current spreads through GAP junctions
Ca++ current travels mostly through
Ltype Ca channels
What contributes to slower pacemaker activities of SA and AV node and slower spread of depolarization btwn neighboring cells causing delay btwn SA and AV nodes?
Ca+ Current
In atrial and ventricle cells, channels rapidly _____ and slowly _____
active
inactivate
What contributes to the Repolarizing K+ current seeing during phase 3
Two currents contribute to Ik
Ikr- : rapid component
Iks- : slow component
Thus Ik slowly activates but doesn’t inactivate
What happens during Early outward K+ current?
Atrail and ventricle cells – activated by depolarization resulting in rapid inactivation
Part of phase 1
What happens during G protein activated K+ current?
Inward K+ current mediated by GIRK K+ channel and is regulated by Ach!!!!
Where are GIRK K channels prominent
in SA and AV nodal cells. When activated by Ach… get decrease in pacemaker rate and slows conduction rate through AV node
ATP sensitive K+ channels that play a role in electrically regulating contractile behavior
K ATP current
What’s ‘funny’ about the If current?
They are not activated by depolarization but activated by HYPERPOLARIZATION during phase 3
–result is slow activation, and slow inward depolarizing current (doesn’t inactivate)
Where are the If current channels found
SA, AV, PKJ
What does the If channel conduction?
Both Na+ and K+ thus it’s nerst potential is about -20mV (between K+ and Na+ potential)
Rough idea of ion conductance during Action potential
See that K is mostly outward rectifying except at phase 4
Na inward during phase 0
Ca+ is inward:
Ltype during 1 and 2
T type during 1
Primary intinsic pacemaker
Has spontaneous depolarization leading to AP generation
SA node
What makes SA our pacemaker?
Other cell types (AV, PKJ) have intrinsic pacemaker, this guy has fastest intrinsic spontaneous depolarization, thus dominant (60-100 bpm)
Electrical synapses connecting cardiac myocytes; allows intracellular flow from cell to cell
Gap junctions
Current spread determined by _____
Ohms law
directly proportional to voltage difference between cells and inversely proportional to resistance btwn cells
V= IR
Secondary pacemaker and introduces delay between atrial and ventricle contraction
AV node
Speed of AP upstroke divides cells into slow response ______ and fast respsonce cells____
slow = SA, AV, nodal cells
fast = atrial and ventricle myocytes, PKJ
What determines cardiac fnx?
Electrical excitation!
PKJ fibers originate in AV node with Bundle splitting into left and right bundles.
The left further divides into:
left anterior fasicle and left posterior fasicle
PKJ has what type of conduction
very rapid but slow intrinsic pacemaker activity
Phase 4 is characterized by gradual, spontaneous depolarization due to pacemaker current:
If (funny current)
Threshold potential is reached at _____ in pacemaker cells followed by upstroke of AP
-40mV
Why is the upstroke phase 0 less rapid in pacemaker cells then in nonpacemaker cells?
Bc current represents Ca++ influx through slow Ca++ channels
Whats the difference between slow nodal and fast nonnodal cardiac AP
Slow: SA and AV nodal cells~~ RMP is -40 to -70 mV with AP upstroke of 1-10V/sec; and slow conduction
Fast: atrial/ventricle/PKJ fibs~~ RMP s -80 to -90mV with AP upstroke of >100/500 V/sec faster conduction
Why is there a difference in conduction between fast and slow cardiac AP cells?
Due to fast Na+ in the atrial/ventricle/PKJ
And the spontaneous slow opening Ca+ channels in the nodal pacemaker cells
What causes the spontaneous depolarization in the SA node?
Pacemaker Channels I (HCN)
HYPERPOLARIZATIONG activated, cyclic nucleotide gated and cation selective; Ehcn~ 0 mV
Ach released from Vagus (PNS) onto SA and AV node has what affect on:
on If
on GIRK
on Ica
On If: in SA node and reduces steepness of phase 4
Ach opens GIRK–> thus increase K+ conductance and makes diastolic potential more negative
ACh reduces Ica–> reduces steepness of phase 4 and moves threshold to more positive value
What effect does ACh have in the AV node
simular to that in the SA; but mostly it will sloooow down conduction velocity. Mainly by decreasing Ica thus threshold is more positive and more difficult for one cell to depolarize neighbors
Nepi is released from SNS and acts on beta-adrenergic receptors in SA and AV node: How does it affect:
If
Increases If– thus increases steepness of phase 4 (vs Ach which has opp effect)
Nepi is released from SNS and acts on beta-adrenergic receptors in SA and AV node: How does it affect:
Ica
Ica is increased thus steepens phase 4 and makes threshold more negative (vs ACh which reduces Ica and decreaes steepness and moves threshold +)
Nepi is released from SNS and acts on beta-adrenergic receptors in SA and AV node: How does it affect:
What affect does Nepi have on maximum diastolic pressure
NONE! Ach makes diastolic pressure potential more negative and Nepi doesn’t do shit
What effect does Nepi have on atrial and ventricular cells?
ionotropic effect: Increase Ica–> increased Ca+ influx–> CICR from SR–> increases senstivity of Ca release channel (Ry-re) and enhances SR pumping to stimulate SERCA to store more Ca+
Overall affects of how PNS ACh release alters heart rate of nodal depolarization
- Decreaes RATE of depolarization: decrease in If
- Decreaes maximium diastolic pressure: increase in Ik
- Increase in threshold potential: decrease in Ica
***ALL three cause more time to reach threshold
When is cell unexcitable to simulation
ARP: absolute refractory
Refractory period is brief time before ARP (when localized depolarization wont propagate). At RP what can happen
stimulation produces a weak AP that propagates, but slower then usual
When can a weaker then normal stimulus can trigger AP
At supranormal period
Impuluse conduction: the speed of depolarization depends on:
resting potential
Normal RP gives rapid rise to phase 0
less negative RP results in slower rise of phase 0 and lower maximum amplitude of AP
Affect of temperature on heart
increases SA node firing via slope of phase 4
see 10 beats/min with 1 degree elevation
What effect does Hyperkalemia have on heart
increase K+ increaes resting potential: see fast inward current that reduces rate of rise and amplitude of AP… slooooows conduction
Reduces P wave amplitude
widens P-R inderval
decreaes force of cnx
How does hyperkalemia accelerate repolarization
shortens duration of AP
shortens Q-T inveral
see tall T wave peaks
What happens in severe hyperkalemia
Disapperance of P wave, AV nodal block and V-fib and sudden death
What affect does HYPOkalemia have on
RMP:
AP:
T wave
PR and QT intervals:
RMP is decreased
slowing of repolaization and prolongation of AP
T Wave is flattened
P-R and QT intervals are prolongued
What happens in severe HYPOkalemia
cause AV block and ventricular fibrilation
What effect does HYPOcalcemia have on the myocardial action during AP?
shortens ventricular AP duration via shortening phase 2 of AP–> thus shortens ST segment == shorter Q-T interval
What effect does HYPERcalcemia have on the myocardial action during AP?
Prolongues phase 2 of AP and prolongues ST segment thus QT interval
Imbalance of what two electrolytes can have serious effects on the heart?
K and Ca
Mineralcortacoids are key in maintaining:
Na and K+.. in ECF: loss of mineralcorticoids can cause lifethreatening abnormalities in electrylyte and fluid balanc
As + charge enters heart during depolarization we get a flow of + charge downstream via gap junctions: this produces….
discharge of extracellular + charged ions associated with cell membrane and flow of + extracell charge upstream
Intracellular and extracellular current must be:
equal and opposite
How is ECG generated?
Extracellular currents produce instantaneous electrical vectors that the ECG measures together throughout the heart
P wave is:
atrial depolarization
QRS complex is
ventricular depolarization
T wave is
ventricular repolarization
PR is:
AV node conduction
QT interval is
ventricular depolarization and repolarization
Phase 0
Na+ influx fast Na+ channel or Ca++ influx in pacemaker cells triggered by depolarization
Phase 1
Transient repolarization K+ efflux
Phase 2
Ca++ influx and K+ efflux, plateau d/t small net current flow
Phase 3
Repolarization mediated by K+effux, decline Ca++ influx. Domiant repolarizating current is Ikr; rapidly activiating repolarization current carried by hERG-KCNE2 gene product (can be targeted by lots of drugs causing AP duration prolongation)
Iks or slow acting repolarizing current aslo contributes to phase 3
Phase 4
Restoration ionic balance between Na/KATPase exchanger and Ca++ATPase
nonpacemaker cells return to RP
slow phase 4 depolarirzation in pacemaker cells
Funny current If deporarlizing current SA node, influx Na+ and K+
Function of K+ channel blockers
Increase AP duration and ERF or phase 3
Effect of Ca++ channel blockers
L-type Ca, slows rate in SA and AV nodes
Na channel blockers
reduce phase 0 and slope of depolarization
Action of Beta Blockers
prevent Ca entry into cell
Decrease: HR, conduction velocity, strength of contraction
–Used to tx lots of CVS conditions: HTN, angina or MI and arrythmias
