Physiology of Cardiac Muscle

Electrophysiology
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 INTRODUCTION
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Systole, or contraction, is the mechanical event that occurs as a result

of electrochemical events that take place in the myocardial muscle
tissue.

Movement of electrically charged particles across the wall or membrane

of a cell creates voltage differences between tissue at rest and tissue that
has been electrically activated.

Electrophysiology examines the electrical behaviour of a single cell

in a conduction medium, as it is at rest, during electrical stimulation,
and during the recovery period following stimulation.
INTRINSIC CONDUCTION SYSTEM
Cardiac autorhythmic cells in the intrinsic conduction system generate action
potentials that spread in waves to all the cardiac contractile cells.

This action causes a coordinated heart contraction.

Of all the cells in the body, only heart cells are able to contract on their own without
stimulation from the nervous system.

GAP JUNCTIONS
Action potentials generated by autorhythmic cells create waves of depolarization that
spread to contractile cells via gap junctions.
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EXTRACELLULAR AND INTRACELLULAR MOVEMENT
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Ion - positively charged

particle (cation) or negatively
charged particle (anion) that is
Ion Extra- Intra-
capable of transmitting a Na+ 140 10
current to other ions.
The fluid inside the cell
K+ 4 145
(intracellular) and fluid on the Ca+ 2 0.2
outside of the cell (extracellular)
have specific concentrations of
positively and negatively
charged electrolytes (ions).
MOVEMENT OF IONS ACROSS A CELL MEMBRANE
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Cells are enclosed by a semi-permeable membrane to allow

specific ions to move passively across.
Selective permeability limits passive ionic diffusion from
one side to the other to specific conditions. Differences in
electrical charge and chemical concentration on each side.
Ions flow through ion-specific channels along the cell
membrane.
These channels are “slow channels” and “fast
channels” depending on the rate of flow of ions, and the
mechanism of activation.
 MOVEMENT OF IONS ACROSS A CELL MEMBRANE
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Passive transport of ions, requiring no energy.

Ions move across cell membrane from an area of high concentration to
an area of low concentration when a concentration gradient exists
“osmosis”
The flow of ions down a concentration gradient is an electrical current.
Sodium and potassium pumps actively transport ions rapidly
across the membrane.
ATP (adenosine triphosphate) is required since pumping sodium
out of a cell and potassium into a cell is against concentration gradients.
 MOVEMENT OF IONS ACROSS A CELL MEMBRANE
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The change in membrane permeability causes movement of electrolyte (

Na+ and K+), this changes the electrical charge intracellular vs
extracellular fluid.
The change in electrical charge caused by electrolyte movement creates
a current.
Travels from cell to cell, conducted from negatively charged cells to
positively charged cells.
 ELECTROCHEMICAL EVENTS FOR CURRENT FLOW
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When a cell membrane is neither responding to or recovering from and

electrical stimulus it is resting or polarized. The intracellular fluid is
negatively charged relative to the extracellular fluid.
MRP (membrane resting potential)- is the electrical potential
gradient that exists across the cell membrane when the cell is at rest.
A polarized myocardial cell has a high level of positively charged
potassium ion and low concentration of sodium ion in the intracellular
space.
The extracellular space has high concentration of sodium and low
concentration of potassium.
POLARIZED
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MRP Develops for 3 reasons:

1) Higher concentration of K+
inside cell
2) Higher concentration of
Na+ & Ca2+ outside cell
3) Cell membrane is more
permeable to K+ than Na+
 MOVEMENT OF IONS ACROSS A CELL MEMBRANE
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A myocardial cell will remain in constant MRP until electrically

stimulated.
The more negative the value the more rapid will be the conduction
velocity of that type of myocardial cell.
MRP exists at Phase 4 of the action potential curve.
A pacemaker cell, due to automaticity does not maintain a
constant MRP.
Pacemaker cells under go slow diastolic depolarization.
 ION MOVEMENT & CHANNELS
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Ion movement depends on 2 major factors:

 Energetic Favourability
 Concentration gradients - Molecules diffuse from areas of higher
concentrations to areas of lower concentrations
 Transmembrane potential (voltage) -refers to the difference in
electrical potential (voltage) across the membrane of a lining cell

 Permeability of membrane to the ion

 Permeability depends upon opening of specific ion channels

 Ion channels vary by 2 functional properties- selectivity & gating

 TYPES OF ION CHANNELS
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1) Non-gated or leak channels are always open

2) Chemically gated channels

open only when stimulated by a chemical
chemical binds to channel stimulating it to open

3) Voltage–gated channels
open by change in membrane potential
 DEPOLARIZATION VS. REPOLARIZATION
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If depolarization reaches threshold, the contractile cells,

in turn, generate action potentials, first depolarizing
then repolarizing.
After depolarization, the cardiac myofibrils in
contractile cells slide over each other resulting in
muscle contraction.
After repolarization these cells relax.
 DEPOLARIZATION
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Cell activation or depolarization, is Phase 0 on the action potential

curve.
Upon stimulation, the cell membrane’s permeability to sodium causes sodium
to diffuse into the cell and potassium to diffuse out.
This action makes the cell voltage LESS NEGATIVE.
If the cell membrane voltage decreases in potential to a specific value
(threshold potential), sodium ions suddenly move rapidly into the cell,
while potassium ions move out of the cell more slowly.
This causes a positively charged intracellular fluid and a positive membrane
potential voltage.
During latter half of depolarization, calcium moves into the cell.
The slope or upstroke of Phase 0 determines the conduction velocity of the cell.
DEPOLARIZED
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 REPOLARIZATION
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Recovery or repolarization of the cells takes place over four phases.

Phase 1
 A brief but rapid early repolarization “overshoot”
 This overshoot occurs because the fast sodium channel has suddenly partially closed –
decrease in sodium influx
 REPOLARIZATION
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Phase 2
 A slow repolarization “plateau”
 Plateau occurs because of the slow flow of calcium ions into the cell, which began at
the end of phase zero and continue during Phase 2. Helps to maintain an ionic
balance.
Phase 3
 Rapid repolarization
 There is a reduction of inward flow of sodium and calcium and a rapid movement of
potassium out of the cell via the active potassium pump
 REPOLARIZATION
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Phase 4
 A constant resting MRP (membrane resting potential) for non pacemaker cells

 For pacemaker cells, they possess automaticity, this is the Phase of

spontaneous depolarization.
 In a muscle cell the membrane potential maintains itself at -90mV –
unchanging.
 Until a stimulus arrives at the cell membrane that is strong enough to cause
and increase in permeability to sodium.
 During this phase ion concentration must be restored, sodium potassium
pumps transport ions back into their original compartments.
 Sodium out, potassium in using ATP

 The more negative the value of MRP the greater the amplitude of the action
potential and its conduction velocity.
 SPONTANEOUS DIASTOLIC DEPOLARIZATION
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Cells that possess automaticity do not have constant MRP.

The transmembrane resting potential becomes gradually less negative
until it reached the cells critical threshold potential. Once reached, the
cell spontaneously depolarizes.
Phase 4 repolarization of a pacemaker cell does not maintain a constant
MRP because potassium outflow decreases while sodium and calcium
move into the cell.
The result is a slow diastolic depolarization as the cell becomes less
negative.
The steeper or more rapid the rise of the slope of Phase 4, the greater the
automaticity (faster impulse generation) ex. SA node
 CARDIAC ACTION POTENTIAL
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The cardiac action potential is the change in

cardiac intracellular voltage due to
depolarization and repolarization over time.
Action potential diagrams represent
recorded electrical changes within a specific
single cell.
The electrical activity of a cell has a
characteristic configuration based on the
type of cell and degree of automaticity,
conductivity and excitability that it
exhibits.
 ACTION POTENTIAL
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 Fast and slow response

 Fast response is more negative
 Greater up-slope, amplitude, and overshoot
 Slow conduction increases rhythm disturbances
 THRESHOLD POTENTIAL
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The critical value of voltage of the

transmembrane potential at which a cell
will generate a propagating action
potential, once the cell has been
depolarized to that voltage.
If the voltage does not depolarize to
threshold potential, no response will occur.
Once the voltage reaches threshold
potential the cell voltage automatically
proceeds through the phases. The “all or
none law” of cardiac muscle cells.
 THE REFRACTORY PERIOD
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 The action potential curve is divided into 3 periods, these

describe the cells responsiveness to an electrical stimulus
 Under normal conditions cardiac cells are not depolarized
until they have had time to recover from the previous
depolarization.
 Absolute or effective refractory (ERP)– cell will not respond
to any other stimulus for a specific period of time no matter how
strong the stimulus. ERP includes Phase 0,1,2 and up to middle of 3.
 Relative refractory period – stronger than normal electrical
impulse may cause a cell membrane to depolarize. RRP includes the
end of Phase 3.
 Supernormal period – Period close to threshold potential,
weaker impulses may be able to cause the cell membrane to
depolarize
 THE REFRACTORY PERIOD
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Without a long refractory period, the impulse would keep going around
the heart in a circle, depolarizing at regular and rapid intervals.
Myocardial muscle cells remain in refractory for approx. 300 msec after
depolarization.
Once impulse meets tissue in refractory it cannot repeat the circuit.
 FAST RESPONSE ACTION POTENTIALS
Cardiac contractile cells
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Non-nodal action potentials,

sometimes referred to as "fast
response" action potentials,
are characteristic of atrial and
ventricular myocytes, and the
fast-conducting Purkinje
system in the ventricles.
These action potentials have a
true resting potential, a fast
depolarization phase, and a
prolonged plateau phase.
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 FAST RESPONSE ACTION POTENTIALS
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 MRP is about – 90 mV, the most

negative of all the cardiac cells.
 In Phase 4 the MRP is constant until the
cell is externally stimulated.
 Rapid rate of rise in Phase 0 and largest
amplitude to make conduction through
these cells relatively rapid.
 Phase 1 “overshoots” into the positive
potential range to + 20 mV.
 Phase 2, the plateau phase, where
repolarization is slow and prolonged.
 Phase 3 there is rapid repolarization.
 IONIC BASIS OF THE FAST RESPONSE

Phase 0 - Rapid depolarization

 Anything that raises the resting potential beyond threshold (-65
mV) will cause an action potential.
 Phase 0 due to Na influx.
 Fast Na channels (voltage gated) open as membrane voltage
becomes less negative. – 65 mV
 Na flows in due to the electric gradient until membrane voltage =
0 then concentration gradient takes over.
 Na channel closes due to the rising membrane voltage
 Na channels remain closed until partially repolarization (effective
refractory period).
 IONIC BASIS OF THE FAST RESPONSE

Phase 1 - Early rapid repolarization

 Following rapid Phase 0 depolarization into the
positive voltage range, brief current of
repolarization returns the membrane potential to 0
mV.
 This is caused by efflux of K through a transiently
activated K channel (voltage gated)

Phase 2 - Plateau phase

 Long phase mediated by the balance of outward K
current in competition with an inward Ca current,
which flows through specific L-type calcium
channels.
 IONIC BASIS OF THE FAST RESPONSE

 Phase 3 - Final rapid repolarization

 Repolarization occurs when K Efflux exceeds influx of Ca.
 Final phase of repolarization that returns
transmembrane voltage back to resting potential of -90
mV.
 Repolarization (slower process than depolarization)

 Phase 4 – Resting Membrane Potential

(Spontaneous Diastolic Depolarization for
pacemaker cells -90 mV
 Na + and Ca2+ channels are closed
 Interval between repolarization to the next action
potential
 Pumps restore ionic concentrations
 SLOW RESPONSE ACTION POTENTIALS
Autorhythmic cells
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 Nodal action potentials, sometimes referred

to as "slow response" action potentials, are
characteristic of action potentials found in
the sinoatrial node (SA) and atrioventricular
(AV) node.
 These action potentials display
automaticity, or pacemaker activity, and
therefore undergo spontaneous
depolarization.
 Their depolarization phase is slower and
they have a shorter action potential duration
than non-nodal, fast response action
potentials. They have no phase 1 or phase 2.
 SLOW RESPONSE ACTION POTENTIALS
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 MRP is -60 mV, the least negative of all

cardiac cells
 The slope on Phase 4 has the steepest rise
 Phase 0 has the slowest rate of rise and
lowest amplitude because the impulse is
conducted slowly. This is due to fast sodium
channels being inactivated. Upstroke relies
on Ca influx through slow Ca channels.
 Phase 1 has a diminished or absent
overshoot, does not move into positive
range.
 Phase 2 and 3 repolarization is gradual and
even, there is no plateau phase.
 IONIC BASIS OF THE SLOW RESPONSE

 Phase 4 is not flat, but has an upward slope, representing

spontaneous gradual depolarization.
 This spontaneous depolarization is a result of the
pacemaker current or “funny current”
 This current is predominately carried by Na ions
 This Na channel opens during repolarization of the cell, as the
membrane potential approaches its most negative.
 This inward flow of positive charged Na causes the membrane
to become less negative during Phase 4, depolarizing cell to
threshold voltage.
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ECG records depolarization

and repolarization

• Atrial depolarization
• Ventricular
depolarization
• Atrial repolarization
• Ventricular
repolarization
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 NORMAL SEQUENCE OF CARDIAC DEPOLARIZATION
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Electrical activation of the heartbeat is normally initiated by the SA

node.
Impulse spreads to surround atrial muscle via intercellular gap
junctions.
Electrical signal reaches the AV node, a delay in conduction is
encountered.
After the AV node the cardiac action potential spreads into the rapidly
conducting bundle of His, bundle branches and Purkinje fibers. Which
distribute the electrical impulse to the ventricular muscle.
Phase 0 = Na+
Phase 1 = K+
Phase 2 = Ca++ 41
Phase 3 = K+

Action Potentials in Cardiac Myocytes

Action Potentials in Pacemaker Cells