Chapter 2: Electrical Activity of the Heart

Cell Membrane Potentials

What is resting membrane potential?

Electrical potential of a resting cell

• measured with a microelectrode

• outside of the cell is 0 mV

Cell Membrane Potentials

What is the resting potential of a ventricular MYOCYTE (Em)?

90mV

Cell Membrane Potentials

How was the resting membrane of a ventricular myocyte determined by?

1. the concentration of + and - ions across the cell

2. relative permeability of the cell membrane to these ions

3. ionic pumps that transport ions across the cell membrane

Cell Membrane Potentials

What are the movement of ions in and out of the myocyte?

• high concentration of K+ inside the cell diffuses out

• high concentration of Na+ outside the cell diffuses in

• high concentration of Ca++ outside the cell and diffuses in

Cell Membrane Potentials

Why is K+ important?

It is the most important ion in determining the resting membrane potential

Cell Membrane Potentials

What directs the concentrations of ions?

Activity of energy-dependent ionic pumps and semi-permeable membrane

Cell Membrane Potentials

When K+ diffuses out, what happens to the cell?

As K+ diffuses out of the myocyte, it leaves behind negatively charged particles, creating a potential difference

Cell Membrane Potentials

Why is the equilibrium potential important and what is it dependent on?

It is the membrane potential that is necessary to oppose the outward movement of an ion down its gradient

• most important is the equilibrium constant for K+ because it keeps the K+ from diffusing down its chemical gradient and out of the cell

Cell Membrane Potentials

How are ionic gradients maintained?

• concentration gradients maintained via energy-using ionic pumps

• require ATP

• the Na+/K+ pump is electrogenic and pumps 3 Na+ for every 2 K+ (pumping more positive out of the cell turns it into a negative potential within the cell)

Cell Membrane Potentials

What happens if the Na+/K+ pump stopped working?

• If pump inhibited by diogoxin, the Na+ accumulates within the cell and intracellular K+ falls, resulting in a less negative resting membrane potential

Cell Membrane Potentials

What must be removed from the cell following a depolarization and how?

Ca2+ needs to be extracted from the cell via 2 mechanisms

• ATP-dependent Ca++ pump that actively pumps Ca++ out and generates a small negative potential

• NA+/Ca++ antiporter exchanger that can be flipped depending on membrane potential, and exchanges 3 Na+ for every 1 Ca+

Ion Channels

What are the 2 types of ion channels?

• voltage-gated: respond to changes in membrane potential (ex: Na+, K+, and Ca++ during cardiac action potentials)

• receptor-gated: respond to chemical signals through membrane receptors (ex: ACh binding to open special K+ channels)

Ion Channels

At resting membrane potentials, what happens to the ion channels?

Na+ gates are closed

• m gate (activation gate) is blocking the opening on the membrane

• h gate (inactivation gate) is open during this time

Ion Channels

When there is a disruption in voltage (depolarization), what happens?

• m gates become rapidly activated and open, allowing Na+ in through its chemical gradient

• as the m gates open, the h gates begin to close slowly (m gates open more rapidly than h gates closing so this allows Na+ to briefly enter the cell)

Ion Channels

After a few milliseconds, what happens to the channels?

• the h gate closes and the flow of Na+ stops

Ion Channels

What happens finally to the ion channels?

• at the end of repolarization, the m gates close, and the h gates open again

Ion Channels

When is the refractory period here?

• during the inactivated stage when h gate closes. this is when it is impossible to depolarize the cell again to have another depolarization

Ion Channels

What happens to ion channels during partial depolarization?

• fast Na+ channels respond differently

• partial depolarization causes the closing of h-gates, inactivating the Na+ channel

• the more the cell depolarizes (partially), the more inactivation of the Na+ channels

• so during these slow depolarizations, more time allows for the closing of h gates as the m gates open

  • go from straight from resting to inactivated

Action Potentials

When does action potentials occur?

• when the membrane potential suddenly depolarizes, and then repolarizes

Action Potentials

What are the two types of cardiac action potentials?

• non-pacemaker

  • triggered by nearby cells (not spontaneous)

  • cardiac myocytes

• pacemaker

  • spontaneous

  • nodal cells (SA and AV node)

Non-pacemaker Action Potentials

Do non-pacemaker cells have a true resting membrane?

non-pacemaker cells have a true resting membrane potential that remains near the equilibrium potential for K+

Non-pacemaker Action Potentials

What are the different phases?

• phase 4: resting membrane potential

• phase 0: rapid depolarization caused by the conductance of Na+

  • initiated by the increasing Na+ into the cell, and moves the membrane potential away from the K+ equilibrium membrane potential, and closer to the Na+ equilibrium membrane potential

• phase 1: initial repolarization

  • caused by the opening of special (outward) K+ channels

  • also caused by inactivation of Na+ channels

• phase 2: plateau phase

  • delayed repolarization due to slow influx of Ca++ which occurs through long-lasting L-type Ca+ channels

• phase 3: repolarization

  • K+ conductance increases and Ca++ conductance decreases

Non-pacemaker Action Potentials

Label the curve with what is happening at the phases in simple terms. What is ERP and when is that?

• phase 4: -90 mV resting

• phase 0: rising above 0 mV and is when Na+ enters

• phase 1: dips closer to 0, and starts repolarization with K+ exits

• phase 2: delay in repolarization as Ca2+ moves into the cell

• phase 3: dips all the way down and near -90 mV because K+ efflux is greater than Ca+ influx

• phase 4: back to -90 mV resting

Non-pacemaker Action Potentials

What is ERP and when is that?

ERP is the effective refractory period, which is stages when a new action potential cannot be initiated

• phases 0, 1, 2, and part of 3 = unexcitable

Non-pacemaker Action Potentials

What is ARP and when is that?

• absolute refractory period

  • phases 0, 1, and most of 2

  • h-gates are closed, so no new action potentials can be produced

  • this serves to limit the amount/duration of action potentials

  • also allows the heart to have adequate time to fill and eject blood

Non-pacemaker Action Potentials

What is RRP and when is that?

• relative refractory period

  • final part of phase 3 and part of 4

  • myocytes are capable of new action potentials, but a lot of stimuli are required

  • Na+ channels are not fully recovered (only when Na+ channels are fully recovered can the cells become excitable by normal depolarization magnitudes)

Non-pacemaker Action Potentials

Why would you prescribe calcium channel blockers to someone with a high HR?

• high HR means there are short action potentials, meaning more heart beats are fitted in a minute

• this drug can change the length of time that the action potential lasts

  • by blocking Ca++ channels, it prevents Ca++ rush and makes phase 2 slower because Ca++ doesn’t enter as much but enters for longer

  • thus, they can fit less action potentials/contractions per minute

Pacemaker Action Potentials

Do pacemaker cells have a true resting membrane?

• no, pacemaker cells do not have a true resting membrane due to leak channels

Pacemaker Action Potentials

What is the rate of depolarization in comparison to non-pacemaker cells? Why?

• pacemaker action potentials driven by the slow, inward Ca2+ currents (L-type Ca2+ channels)

• so, it is slower compared to the “fast response” from non-pacemaker cells’ fast Na+ currents

Pacemaker Action Potentials

What sets the pace?

• Cells in the sinoatrial (SA) node

Pacemaker Action Potentials

What else can set the pace, but…?

• Atrioventricular (AV) node is also capable

  • this happens when SA node is slow/fails to reach the AV node

• normally, there is “overdrive suppression” where SA node inhibits the AV by firing faster

  • but, if SA node slows/ fails, then overdrive suppression is gone, and secondary pacemakers can take over the heart’s main pacemaker

Pacemaker Action Potentials

What is ectopic focus?

• when the AV node takes over SA node and becomes the heart’s main pacemakers

Pacemaker Action Potentials

What are the phases of pacemaker action potentials?

• phase 0: upstroke of action potential

  • voltage opens the L-type Ca++ channels, allowing increased Ca++ to flow (slowly) into the nodal cells

• phase 3: repolarization

  • depolarization from phase 0 causes voltage-gated K+ channels to open, and K+ leaves the cell

  • depolarization also causes Ca++ channels to become inactivated, decreasing Ca++ conductance

• phase 4: spontaneous depolarization

  • phase of repolarization is restricted because K+ channels start to become

Pacemaker Action Potentials

In the repolarized states (phase 4), how is there a slow tick of depolarization?

• these funny currents are from the slow inward movement of Na+ throughout the whole phase 4

  • movement of Na+ into the cell contributes to depolarization

• in second half of phase 4, there is a small increase in Ca++ conductance through T-type Ca++ channels

Pacemaker Action Potentials

What is the importance of T-type Ca++ channels?

• if T-types are blocked, there will be no beating, and will die

• it opens briefly at a very negative voltage

• cannot be blocked by classical L-type Ca++ channels

Pacemaker Action Potentials

How do calcium channel blockers affect pacemaker cells?

• since pacemakers’ depolarization depends on Ca++, with low concentration of Ca++ influx, the phase 0 will take a long longer

• so, there will be fewer potentials per minute, and shorter rate of conductance means slower HR

Ca++ Channel Blockers

What is dromotropy and chromotropy?

• dromotrophy: slow conductance rate

• chromotropy: rate of depolarization of nodes

Regulation of SA Nodal Pacemaker Activity

Without any external factors, what is the intrinsic firing from the SA node?

• 100 bpm

Regulation of SA Nodal Pacemaker Activity

However, HR can range below 50 and to more than 200. How?

• adjustments are made by the autonomic nerves acting on the SA node

• vagal tone HR <100, happens at low resting HR and it is more dominant than the sympathetic influences

• vagal withdraw + sympathetic activity: HR > 100 happens when increased sympathetic activity (such as NE binding to beta-adrengeric receptors to increase Ca++ and make depolarizations faster)

Regulation of SA Nodal Pacemaker Activity

What is chronotropy?

• chronotropy is the adjustment in HR

  • + chronotropy = increased HR

  • - chronotropy = decreased HR

Regulation of SA Nodal Pacemaker Activity

Autonomic control of HR can be influenced by what factors?

• increase/decrease of the slope of phase 4

• alter the threshold voltage for triggering phase 0

• alter the degree of hyperpolarization following phase 3

Regulation of SA Nodal Pacemaker Activity

What happens if NE is released from sympathetic nerves?

• binds to beta-adren receptors and activates the G-protein signaling pathway to ultimately increase Ca2+ influx

• this increases slope of phase 4 and lowers threshold to depolarize in phase 0

• increased chronotropy due to accelerated depol and repol, and shortens the overall cycle length

Regulation of SA Nodal Pacemaker Activity

What happens if ACh is released by vagal nerves?

• binds to M2 receptors and decreases G-protein signaling pathway, which ultimately decreases Ca2+ influx

• this decreases slope of phase 4 because it inhibits “funny currents,” and also makes threshold to depolarize in phase 0 higher

• decreased chronotropy due to slower depol and repol

Factors increasing or decreasing SA node firing

Arrhythmias: Abnormal Automaticity

What happens if fast Na+ channels are somehow blocked in cardiac myocytes?

• if blocked, cardiac myocytes can behave similarly to nodal cells

  • slope and amplitiude of phase 0 are depressed

  • depolarization is brought on by L-type Ca++ channels

  • could result in spontaneous action potential generation

Arrhythmias: Triggered Activity

How does triggered activity happen?

• nonpacemaker cells can generate action potentials during abnormal times (phase 3 or 4)

  • early afterdepolarization happens in phase 3 and occurs bc of the slow Ca2+ influx (since Na+ channels are inactive here)

  • delayed afterdepolarization happens later in phase 3/early phase 4

Electrical Conduction within the Heart

How are action potentials spread within the heart?

• via cell-to-cell conduction

  • cells joined together by low-resistance gap junctions located at intercalcated disks

  • leads to cell progagation

Electrical Conduction within the Heart

1 → 2 → 3 → 4 → 5 → 6

1. atria: depolarizes rather fast (0.5)

2. atrial muscle: connective tissue separates atria from ventricles (not a good conductor)

3. AV node: action potentials can only enter the ventricles through the AV node

• action potential is slowed down to 0.05 to allow sufficient time to complete atrial depol, contraction, and emptying of blood into ventricles before ventricular depola/contraction

4. Bundle of His: action potential leaves AV node to the ventricle base called the bundle of His at a high speed (2) and splits into right and left bundle branches

5. Ventricular muscle

6. Purkinje fibers: branches from bundle of His divide into a system of purkinje fibers, which is the final site for cell-to-cell conduction. has the highest speed of 4

• purkinje fiber cells connect with ventricular myocytes

Electrical Conduction within the Heart

What are cell-to-cell conduction regulated by?

• Intrinsic and extrinsic factors

• Intrinsic

  • electrical resistance between cells

  • nature of the action potential (rate of depolarization in phase 0 because the more rapidly a cell depolarizes, the quicker the adjoining cell will too)

Problem 2-2

• even though the Na+ channels are partially inactivated, the Na+ will still attempt to reach threshold for depolarization

• with less Na+ channels, there are less Na+ entering the cell, which will lead to a prolonged phase 0

• it will thus take longer than normal and decrease conduction velocity within the ventricle

Abnormal Conduction

What happens if electrical activation of the heart doesn’t follow the normal path?

• arrthythmias and inefficiencies will appear

  • ex of ineffiency if problem is AV node is blocked: ventricular depolarization will have to rely on slow cell-to-cell conduction between myocytes

Electrical Conduction within the Heart

What is an ectopic beat?

• one that occurs (originates) in a location other than the SA node

Tachycardia Caused by Reentry

When does reentry occur?

• when conduction pathway is stimulated prematurely by a previous action potential

• leads to a rapid, cyclical reactivation

Tachycardia Caused by Reentry

What should happen normally?

• in a single purkinge fiber, it has 2 branches (left and right)

• the action potential would divide into 1 and 2, and travel down

• some of the action potential would travel to the left or right to excite myocytes

• some of the action potential from left and right would meet at a common ground (3) to cancel each other out so that a reentry loop would not occur

Tachycardia Caused by Reentry

What happens in a reentry?

• there is a partial conduction block, where part of the tissue is dead

• when action potential travels down the branches of purkinje fiber, it continues to path 1, but not path fully 2 because of the partial blocked dead tissue

• action potential from path 1 cannot get canceled out because of the partial dead tissue blocking the traveling in path 2

• thus, action potential travels the other side of the dead tissue and reexcite the cells that are beginning to repolarized

  • this leads to early afterdepolarizations

  • this is called a reentry loop because cells from SA node are depolarized by the same SA node pace without a new pace

Tachycardia Caused by Reentry

How would you fix a reentry?

• can use Ca2+ channel blocker drugs to extend refractory period in non-pacemaker cells so when that same action potential re-enters, it will hit a cell that can’t be reactivated again

Global & Local Reentry

What is a global reentry loop?

• AV node is excited without the SA node

• action potential goes to ventricles without the purkinje fibers, and goes via the bypass tract (bundle of kent). then, goes back up to reexcite the AV node

The Electrocardiogram

What is the P wave?

• atrial depolarization

The Electrocardiogram

Can we see the repolarization of the P wave on an ECG tracing?

• we cannot see the repolarization of the P wave on tracing because it is masked by ventricular depolarization

The Electrocardiogram

What is the QRS complex?

• ventricular depolarization

• happens very fast

The Electrocardiogram

What is the T wave?

• ventricular repolarization

• lasts longer than QRS depolarization

The Electrocardiogram

What is the PR segment?

• isoelectric (zero voltage) for a bit between atrial and ventricular depolarization

• time for action potential to travel to AV node

The Electrocardiogram

What is the ST segment?

• squeezing/active ejection from ventricle

The Electrocardiogram

What is the QT segment?

• entire duration for ventricle to eject, contract, and relax

  • ventricular depolarization and repolarization

The Electrocardiogram

Elevation/depression of what is important?

• elevation/depression of ST segment is important

The Electrocardiogram

What are the normal duration of a P wave, QRS complex, T wave, PR interval, ST segment, and QT interval?

• P wave = 0.08-0.10 s

• QRS complex: 0.06-0.10 s

• T wave: cannot be measured

• PR interval: delay 0.12-0.20

• ST segment: cannot be measured

• QT interval: 0.20-0.40 (but can be changed based on action potential duration)

ECG Interpretation

When is the heart in sinus rhythm?

• when P waves (atrial depolarizations) lead directly to QRS (ventricular depolarizations) in a 1 to 1 fashion

  • basically ventricular depolarization is triggered by atrial

ECG Interpretation

What is sinus tachycardia and sinus bradycardia?

• sinus tachycardia is 100+ bpm

• sinus bradycardia is < 60 bpm

ECG Interpretation

What is normal stuff coming from QRS complex?

• amplitude greater than 0.5 mV in at least one standard lead

  • upper limit of normal amplitude is 2.5 to 3.0 mV

• small septal Q waves amplitude less than 1/3 of the amplitude of the R wave

ECG Interpretation

What is normal stuff coming from ST segment?

• isoelectric, slanting upwards to the T wave

• can be slightly elevated (up to 2 mm)

• never normally depressed greater than 0.5mm in any lead

ECG Interpretation

What is normal stuff coming from T wave?

• normally rounded and asymmetrical with a more gradual ascent than descent

• isolated T wave inversion is generally normal in adults

ECG Interpretation

Atrial flutter?

• even saw-teeth

• different clusters of atrial depolarized but independent of the SA node

• “irregularly regular”

ECG Interpretation

Atrial fibrillation?

• further deinvolvement of atrial depolarized state

• individual cells are depolarizing together

• “irregularly irregular”

ECG Interpretation

First-degree AV block?

• P coupled to QRS but AV nodal delay, making intervals longer

ECG Interpretation

Second-degree AV block (2:1)?

• every two P wave is a QRS wave

• half of the action potentials are blocked by the AV node

ECG Interpretation

Third-degree AV block?

• complete AV nodal is blocked

• cannot predict when P wave would become a QRS

ECG Interpretation

Premature Ventricular Complex?

• has global reentry loop

• normal until a lot happens

ECG Interpretation

Ventricular Tachycardia?

• ventricular coupling is not driven from atrial coupling

• no P/T waves are visible because ventricular rate is so high

ECG Interpretation

Ventricular fibrillation?

• filling so low that cannot supply to body

• no contractions as ejection from ventricle stopped

Volume Conductor Principles & Rules of Interpretation

What are 3 things that can influence ECG waveform?

1. location of electrodes on body’s surface

2. conduction pathways & conduction speed

3. changes in muscle mass

Electrical Vectors

What happens when the SA node fires? What does each individual wave represent? What is the sum of all of these?

• a wave of depolarization spreads in several directions throughout the atria

  • each individual wave represents an individual electrical vector

  • by summing each of these individual vectors, you get a mean electrical vector

Electrical Vectors

Direction of the mean electrical vector relative to the positive and negative electrodes determines what?

• polarity of waveform

• magnitude of waveform

Electrical Vectors

Summing mean vectors from several different ECG leads determines what?

• determines the mean electrical axis of the heart

  • used to diagnosically identify left and right deviations

The Electrocardiogram

What are the 5 rules of interpreting an ECG?

1. wave of depolarization traveling towards a + electrode results in a + deflection

2. wave of repolarization traveling towards a + electrode results in a - deflection

3. a wave of depolarization/repolarization perpendicular to an electrode axis produces no net deflection

4. amplitude of the measured potentials depends on the orientation of the + electrode relative to the mean vector

5. voltage amplitude ± is related to the mass of tissue undergoing depolarization/repolarization

The Electrocardiogram

What is happening here?

• no electrical vectors, so the reading is 0

• heart is quiet here

The Electrocardiogram

What is happening here?

• initial electrical transduction

• first region to depolarize is the interventricular septum

• avL will have a negative voltage because the vector is moving away from the + of avL (Q wave of QRS)

• Lead II has no change in voltage because the vector is perpendicular to lead II axis

The Electrocardiogram

What is happening here?

• septum is completely depolarized and apex of heart starts to depolarize

• avL has a small + voltage because the vector is close to being perpendicular to the avL axis but leaning a bit towards avL’s +

• lead II is very positive and has a tall deflection because the vector is almost completely pointing towards lead II’s + (R wave of QRS)

The Electrocardiogram

What is happening here?

• apex and right ventricle completely depolarized and left ventricle is starting to depolarize

• avL has a + voltage because the vector is close to avL’s +

• lead II has a slightly + charge because vector is almost perpendicular to lead II’s axis but slightly leaning towards lead II’s +

The Electrocardiogram

What is happening here?

• last regions of left ventricle depolarized

• avL small + voltage because vector is almost perpendicular to avL’s axis and slightly leaning towards avL’s + charge

• lead II is negative because the vector is pointing away from lead II (S wave of QRS)

The Electrocardiogram

What is happening here?

• ventricles are completely depolarized

• voltage reading is back to 0

The Electrocardiogram

What is the placement of recording electrodes called?

• limb leads: Einthoven’s triangle

Einthoven’s triangle

What are the limb leads and their charges?

• RA (right arm): lead II - and lead I -

• LA (left arm): lead I + and lead III -

• LL (left leg): lead II + and lead III +

• RL (right leg): reference electrode for recording purposes

Einthoven’s triangle

What are the leads?

• Lead I: between RA’s - and LA’s +

• Lead II: between RA’s - and LL’s +

• Lead III: between LA’s - and LL’s +

Axial Reference System

What is the axial reference system?

• three limbs of Einthoven’s triangle broken apart, collapsed, and superimposed over the heart

Axial Reference System

What else is added to the axial reference system?

• 3 leads in addition to the 3 bipolar limb leads

  • aVL - left arm

  • aVR - right arm

  • aVF - foot

Axial Reference System

How do you determine the mean electrical axis?

• can use the 6 leads to estimate mean electrical axis with the axial reference system

• mean electrical axis corresponds to the axis that is perpendicular to the lead axis with the smallest net QRS amplitude

  • aka perependicular to the most biphasic lead

  • can estimate exact axis and if there is an axis deviation

  • will not be able to determine exact axis with this method

Axial Reference System

Draw a circle and label the ranges of the axis deviations

Axial Reference System

Why can axis deviations occur?

• can occur because of the physical position of the heart within the chest

• or changes in sequence of ventricular activation, or ventricular regions are incapable of being activated due to deflected tissue

Axial Reference System

With the axial reference system, walk me through which axial deviation this person might have

• find the most biphasic tracing → aVF

• what is perpendicular to aVF? → lead I

• is lead I’s tracing + and -? → +

• is lead II’s tracing more + or -? → +

• what is perpendicular to lead II? → aVL

• is aVL’s tracing more + or - ? → more +

• is the mean electrical axis closer to lead II or avL? → probably closer to avL because it has taller positive deflections

• is there an axis devation? → could be LAD (left axis deviation)

Axial Reference System

With the axial reference system, walk me through which axial deviation this person might have

• biphasic: aVF

• what is perpendicular to aVF? → Lead I

• is lead I’s tracing + or - ? → -

• is lead III’s tracing + or - ? → +

• what is perpendicular to lead III? →aVR

• is aVR’s tracing + or - ? → more +

• is it closer to lead III or aVR? → closer to aVR since the + deflections are higher

• any possible axial deviations? → could be EAD