Cardiac action potentials arise from the coordinated movement of ions through membrane channels in cardiac cells. The cardiac action potential has 5 phases: rapid upstroke (phase 0) due to sodium influx, early rapid repolarization (phase 1) mediated by potassium currents, plateau phase (phase 2) maintained by calcium and potassium currents, final rapid repolarization (phase 3) due to potassium currents, and resting phase (phase 4) where the cell prepares for the next action potential. Precisely regulated ion channel function underlies the generation and propagation of action potentials and ensures normal cardiac rhythm.

1. CARDIAC ACTION
POTENTIAL
ASWIN R. M.

2. CELL MEMBRANE
Semi permeable - How
moleceules move in & out
of cell ?
CHANNELS
• Aqueous channel
• Conformational change
• Action usually
regulated
• Open to both
environment
• Large number of
molecules diffuse
across
PORES
• Continuously open to
both environment
• No conformational
changes
• Movement both ways
according to
concentration gradient.
CARRIERS & PUMPS
• Not open
simultaneously to both
environments
• Energy dependent
• Limited number of
molecules diffuse
across
• Maintain the
concentration gradients
- Movement can be
against concentration
gradient

3. ION MOVEMENT
Steady state is reached when the magnitude of the chemical and electric
gradients are equal

4. EQUILIBRIUM POTENTIAL
 Also called the, reversal, or Nernst potential of the
channel.
 The potential at which the passive flux of ions resulting
from the chemical driving force is exactly balanced by the
electrical driving force is Given by the Nernst equation
Es =RT/ZF ln [S]2 / [S]1
 T is temperature [kelvin] , R is the gas constant , F is the Faraday constant
 Z is the valence of ion
 [S]2 and [S]1 are the final concentrations of the ion in outer & inner
compartments
 At equilibrium potential net diffusion is 0
 All ions try to reach equilibrium i.e., tries to drive the
membrane potential towards its equilibrium potential
 At RMP, membrane is permeable mostly to potassium ,
hence RMP is close to the EK

5. CONCENTRATION OF MAJOR IONS
Ion Extracellular
Conc
Intracellular
Conc
Ex (mV
Na+ 145 20 +52
K+ 4 135 -92
Ca2+ 2 10-4 +129
CL- 120 10 -64

6. ION CHANNELS
 Electrical signaling in heart  passage of ions
through ionic channels.
 Na+, K+, Ca2+ , and Cl− are the major ions
 Opening of ion channels  selected ions flow
passively down the electrochemical gradient
 Pumps  responsible for mainataining the
electrochemical gradient by active (energy
required) movement of ions
 This flow of current generates excitation and
signals in cardiac myocytes.

7. BASIC TERMS
 Inward current & Outward current
 Rectifying
 Rectifier or diodes allow current only in one direction
 Delayed (s) vs fast/ rapid (r)
 Gating & Inactivation Ion channels may be induced to open
or close (gated) by
 Extracellular and intracellular ligands (ligand gated)
 Changes in transmembrane voltage (Voltage gated)
 Mechanical stress
 The permeability ratio index of a channel’s ionic selectivity
 Ratio of the permeability of one ion type to that of the main
permeant ion type.

8. GATING & INACTIVATION
 Closing and opening of channels
 Voltage, Metabolic, Stretch

9. 3 STATES

10. EXCITABLE TISSUES
Neuron
Skeletal
Muscle
Smooth
Muscle
Cardiac
Muscle

11. ACTION POTENTIAL
 Sudden rise & fall in membrane voltage
in a characteristic pattern
 Depolarization followed by
repolarization
 Passive movement of ions across electro
chemical gradient established by active
ion pumps
 Net current of all open channels [amplitude & direction]
 Depends on 2 factors
 Electromechanical gradient across
 Open Channels
 Fixed time & voltage relationship according to the specific cell type
 Neurons few milliseconds , Cardiac fibers - several 100 milliseconds

12. ACTION POTENTIAL
Independent of size of depolarizing stimulus.
Pattern dependent on individual cell type
Threshold stimulus
“All-or-none” response
Refractory period
But hyperpolarizing pulses in contrast - elicit a response
proportional to the strength of the stimulus.

13. SITES OF ACTION POTENTIAL
GENESIS
Nodal tissue – AV node and SA node
His - Purkinje fibres
Atrial muscle
Ventricular muscle

14. SITES OF ACTION POTENTIAL
GENESIS
 Nodal tissue – AV node and SA node
 His - Purkinje fibres
 Atrial muscle
 Ventricular muscle
PROPERTY SA NODE ATRIAL MYOCYTE AV NODE HIS PURKINJE
VENTRICULAR
MYOCYTE
Resting potential (mV) −50 to −60 −80 to −90 −60 to −70 −90 to −95 −80 to −90
Action potential features
Amplitude (mV) 60-70 110-120 70-80 120 110-120
Overshoot (mV) 0-10 30 5-15 30 30
Duration (msec) 100-300 100-300 100-300 300-500 200-300
V max (V/sec) 1-10 100-200 5-15 500-700 100-200
Propagation velocity
(m/sec)
<0.05 0.3-0.4 0.1 2-3 0.3-0.4
diameter (μm) 5-10 10-15 1-10 100 10

15. CARDIAC ACTION POTENTIAL
2 types : Myocyte & Pacemaker potential
Typical 5 Phases  myocyte potential
• Upstroke or rapid depolarizationPhase 0
• Early rapid repolarizationPhase 1
• PlateauPhase 2
• Final rapid repolarizationPhase 3
• Resting membrane potential and diastolic depolarizationPhase 4

16. FAST & SLOW RESPONSE IN
ACTION POTENTIAL
 Atrial and ventricular muscle , His-Purkinje fibres
 action potentials with very rapid large-
amplitude upstrokes called fast responses.
 SA & AV nodes , many diseased tissue  slow,
reduced-amplitude upstrokes and are called
slow responses
 Fast response  Voltage gated Na Channel (INa)
 Slow responses  slow inward, predominantly
L-type voltage-gated Ca2+ current (ICaL) rather
than by the fast inward INa

17. • INa –Voltage gated Na ChannelPhase 0
• ITo –Transcient Outward K channelPhase 1
• ICaL –L type Ca channel
• IKs –Delayed Rectifier slow K channel
Phase 2
• IKr –Delayed Rectifier rapid K channel
• IKs IK1
Phase 3
• IK1–Inwardly Rectifying K channelRMP
• ICaT –T type Ca channel
• If –Funny (slow) Na channel
Diastolic
Depolarisation

18. RESTING MEMBRANE
POTENTIAL
 Membrane potential when the
cell is not stimulated.
 Horizontal line in most cardiac
tissues
 Cells with automaticity no static
RMP
 Corresponds to equilibrium
potential of K+
 -50 to -90 according to type of cell
 Ventricular myocardium is about -
85 to -95 mV

19. IONS - RMP
 Outward K+ current – Inwardly rectifying K+
channels(IK1 ) -contributes to RMP atrial and
ventricular myocytes, as well as in Purkinje cells.
 Low [K] Voltage leads to less IK1 activity  RMP
less negative more excitability
 Ca- No direct effect but intra cellular Ca can
influence other ions ex: Cl- & Na+/Ca++ exchanger
 Na+ K+ ATPase – 3 Na+ outward and 2 K+ inward
against their gradient.
K+

20. PHASE 0
 Rapid depolarisation phase
 Opening of the fast Na+ channels causing a rapid
increase in membrane conductance to Na+ (INa)
 Membrane potential goes upto the Na+ equilibrium
potential of +60 mV
 Rate of depolarization dV/dt max  rate and
magnitude of Na+ entry into the cell : corresponds
to conduction velocity V Max
 Action potential = Na+ current (INa) is regenerative
 SA node & AV node - Ica
4
0

21. RMP AND Na CHANNELS
 RMP at baseline (-85 mV) all fast
Na+ channels are closed and
excitation will open all of them 
maximum conduction velocity
 Na conduction  time dependent
 Any decrease in RMP (less neg)
some of the fast Na+ channels will
be in an inactivated state insensitive
to opening  conduction velocity
decreases . Ex: Ischemia

22. FAST & SLOW CHANNELS
 In fast response tissues also ICaL is normally activated
in phase 0 by the depolarization caused by the fast
INa. especially in latter part ofupstroke
 However ICa.L << INa  contributes little to the AP
 Significance after the fast INa is inactivated (after
completion of phase 0)  plateau phase
 ICa.L  release of Ca2+ from SR stores  cardiac
excitation contraction coupling
 Recovery of ICaL voltage & time dependent a
phenomenon termed post repolarization
refractoriness
 SA and AV nodal cells remain refractory even after
full voltage repolarization

23. CLINICAL ASPECTS
 Acute MI  depressed form of fast conduction
in centre & slow reponse in border area
 Increase cAMP – Increased Ica L
 CCB – Decreases Ica L
 Class I antiarrhythmics – affects fast channel &
not slow channel

24. BRUGADA SYNDROME
 Most common  AD Loss Of Function SCN5A gene
(encodes for Voltage gated Na channel)
 Polymorphic ventricular tachycardias & SCDs
 Incidence 1-5 / 10 000 ( High in SEAR)
 Na channel blockers [Ajmaline Flecainide and
Procainamide ] used for provocative testing.
 Type 2 & 3 patterns should change to Type 1 pattern
with drug testing

25. BRUGADA DIAGNOSIS
Patients with ST-segment elevation with type 1 morphology ≥2 mm in
one or more leads among the right precordial leads V1 and/or V2
positioned in the second, third, or fourth intercostal space,
Occurring either spontaneously or after provocative drug test with
intravenous administration of sodium channel blockers (such as
ajmaline, flecainide, procainamide or pilsicainide).
2015 ESC Guidelines for the management of patients with ventricular arrhythmias
and the prevention of sudden cardiac death

26. PHASE 1
Shortest phase
Inactivation of the fast Na+ channels
Outward current Mainly K+ and Cl- ions
Na+/Ca2+ Exchanger

27. PHASE 1 OUTWARD K+
 Termed Ito current
 Turned on rapidly by depolarization and then rapidly inactivates
 4-aminopyridine–sensitive transient outward K+ current
 Density and the Recovery exhibit transmural gradients in the left
and right ventricular free wall From epicardium to endocardium
Density decreases
Reactivation progressively prolonged
 Failing Heart - Downregulation of Ito  phase 1 repolarization slows

28. OTHER CURRENTS
 4-aminopyridine–resistant Ca2+ -activated
chloride current ICl.Ca (or Ito2)
 Outward Na+ movement through the Na+/Ca2+
exchanger operating in reverse mode.

29. PHASE 2 - PLATEAU
 Characteristic feature of cardiac myocyte & conducting
system
 Not present in other tissues including cardiac pacemaker
cell
 All ion channels – in a state of resistance ie. slow ion
movement
Outward movement of K+ through the slow
delayed rectifier potassium channels (IKs)
Inward movement of Ca2+ (ICa) through L-type
calcium channels & Na+/Ca2+ exchanger

30. PHASE 2
 Even though gradient of K+ is high after a
depolarization the movement is restricted.
 K1 current inwardly rectified
 Delayed rectifier K current  Rapid (IKr) &
slow(IKs)
 Rapid channels inactivated by the depolarization
current.
 This fast inactivation sensitive to extracellular
[K+]  Accentuated at low extracellular K+
 Hypokalemia  Decreases IKr  Prolongs APD

31. PHASE 2
 Reduced intracellular ATP (e.g. hypoxia,
ischemia), K+ efflux through activated KATP
channels is enhanced shortening the plateau
phase
 Inactivation of the L-type Ca2+ dependent on
intracellular free Ca2+
 Reduced efficiency in inactivation, such as in
myocytes from hypertrophic hearts  delayed
repolarization.

32. PHASE 3 –
FINAL RAPID
REPOLARIZATION
 Terminal repolarization – rapid because of two
currents
 Time-dependent inactivation of ICaL  decrease
in the intracellular movement of positive charges
 Activation of repolarizing K+ currents,
 Including IKs and IKr
 Inwardly rectifying K+ currents IK1 and IKACh
 Membrane potential moves to RMP

33. REFRACTORY PERIOD
ABSOLUTE RP
Second stimulus however
strong fails to evoke a
response.
RELATIVE RP
Second stimulus evokes a
response if it is
sufficiently high (supra
threashold stimulus)
EFFECTIVE RP
Suprathreashold stimulus
 action potential but
not propogated

34. MECHANISM
 ARP Na are in an inactivated
state -
 RRP  sufficient number of Na
channels back to their resting state
– a stronger stimulus can generate
AP
 Cardiac RP (250 ms) very long
compared to other exetitable
tissues (ex: Skeletal muscle – 3 ms)
 Prevents tetany
 Prevents Fatigue
 Diastole >>systole
 Responsible for compensatory
pause after a VPC

35. AFTER DEPOLARIZATIONS
Membrane voltage oscillations
induced by 1 or more preceeding
AP
Clinical conditions or interventions
causing increase in intracellular
positivity
Important role in Arrhythmias
Most of then will not reach threshold potential. If
sufficiently strong – trigger another AD & self perpetuates)
Delayed after depolarizations  Phase 4 after
repolarisation has completed but before next AP
Early after depolarizations  Phase 2 & 3

36. EAD
 Reopening of L type calcium
Channels
 Precipitated by bradycardia &
prolonged APD allowing more Ca
channels to recover.
 Any drug or intervention or
clinical situation causing
intracellular positivity  EAD
 Responsible for lengthened
repolarisation & VT/VF seen in
long QT syndromes

37. DAD
 Increased cytosolic Ca++
 Digitalis toxicity  diastolic
Ca++ release from SR
 β-adrenoceptor stimulation
 Low extracellular [K+]
 Ischemia
 Precipitated in background of
rapid HR

38. PHASE 3 & ARHYTHMIAS
 Congenital disorders (LQTS & other channelopathies)
that prolongs repolarisation  predisposes to
ventricular arrhythmias
 Several drugs inhibit IKr  acquired forms of LQTS
 Macrolides & quinolones Antifungals such as ketoconazole
 TCA SSRI Antipsychotics such as haoloperidol
 Antihistamines such as terfenadine Cisapride
 Class Ia & III antiarrhythmics
 Failing LV myocytes has decreased IK1 activity  ↑s
APD & Resting membrane depolarization.
 Failing cardiomyocytes  Reduction in the outward K+
current  DAD triggered by spontaneous intracellular
Ca2+-release events

39. CHANNELOPATHIES

40. LQTS
 Delayed repolarization of the myocardium, QT
prolongation (QTc > 480 msec )
 Increased risk for syncope, seizures, and SCD in the
setting of a structurally normal heart
 1/2500 persons
 Usually asymptomatic, certain triggers leads to
potentially life-threatening TdP
 50% of SCD usually has prior warning/ family history,
5% SCD- sentinel event.
 Pathophysiology
 EAD R on T  VT/VF
 DAD
 Re entry

41. DIAGNOSIS
SCHWARTZ SCORING
Poi
nts
ECG 1
QTc
2
≥480 ms 3
=460-479 ms 2
=450-459 ms (in males) 1
≥480 ms during 4th minute of
recovery from exercise stress
test
1
Torsade de pointes 3
2
T wave alternans 1
Notched T wave in 3 leads 1
Low heart rate for age 4
0.5
history
Syncope
3
With stress 2
Without stress 1
Family
history
Family member(s) with definite LQTS 5
1
Unexplained sudden cardiac death at
age <30 years in immediate family 5 0.5
Total score
≤1.0 point = low probability of LQTS
1.5-3.0 points = intermediate probability of LQTS
≥3.5 points = high probability of LQTS
2015 ESC Guidelines for the management of patients
with ventricular arrhythmias and the prevention of
sudden cardiac death

42. TEATMENT
 Life style modification
 b blockers in LQTS clinical diagnosis (ecg) [ may be
given in pts with molecular diagnosis alone]
 Sodium channel blockers (mexiletine, flecainide or
ranolazine) add-on therapy LQTS3 patients with a
QTc > 500 ms.
 PPI in cases with sustained pause dependent VT +/-
QT prolongation
 ICD in survivors of cardiac arrest, may be given in b
blocker resistant, considered in high risk groups
[LQT2, LQT3, QT>500ms]
 Left cardiac sympathetic denervation considered for
symptomatic b blocker resistant]

43. CPVT
 Lethal familial disease , manifests in childhood
and adolescence
 Untreated 30% mortality by the age of 40yrs
 Precipitated by exercise especially swimming
 Stress or exercise-induced bidirectional
ventricular tachycardia (biVT) or PMVT
 Pathophysiology Increased Ca2+ release
through defective SR release
 Most common CPVT1 (Ryanodine receptor or
RyR2 gene) also CPVT2 (CASQ2 gene)

44. DIAGNOSIS

45. TREATMENT
 Lifestyle changes
 Beta blocker – all patients , genetically positive
patients with neg exercise testing also.
 ICD – Cardiac arrest , R/c syncope , BiVT
 Flecainide  add on therapy to Beta blocker , If
ICD cannot be implanted , to reduce shocks on
ICD.
 Left cardiac sympathetic denervation 
recurrent syncope or polymorphic/bidirectional
VT/several appropriate ICD shocks
 Invasive EPS  Class III

46. SQTS
 Remarkably accelerated repolarization that is
reflected in a shorter-than-normal QTc [<320
msec]
 Susceptibility to arrhythmias and sudden death
[paroxysmal atrial fibrillation, syncope, and an
increased risk for SCD]
 Syncope 25% pts, Family history of SCD 30% pts,
AF in 1/3rd.
 Most often during Rest or Sleep.
 5 genes
 Gain of function mutations in K channel- KCNH2 [IKr]
(SQT1), KCNQ1 [IKs] (SQT2), and KCNJ2 [IK1] (SQT3)
 Loss of function mutations in ICaL -CACNA1C (SQT4)
and CACNB2b (SQT5)

47. SUMMARY
Phase 0
Phase 1
Phase 2&3
Phase 4
Phase 2&3
Phase 2&3
Phase 2&3
Phase 2&3

48. PHASE 4 DIASTOLIC
DEPLARISATION
 Unstable membrane potential that starts at – 60mv and
slowly depolarizes upwards towards threshold
 The property possessed by spontaneously discharging cells
is called phase 4 diastolic depolarization
 Leads to initiation of action potentials resulting in
automaticity.
 Normal conditions  membrane
potential of atrial and ventricular
muscle cells remains steady
throughout diastole (RMP).
 IK1 responsible for maintaining
the RMP
 Pacemaker cells- No constant
RMP

49. ACTION POTENTIAL IN PACEMAKER
CELL - AUTOMATICITY
•PHASE 4: PACEMAKER POTENTIAL:
•Opening of voltage-gated Na channels
called Funny channels (If or f channels ).
•Closure of voltage-gated K channels.
•Opening of Voltage-gated Transient-type
Ca (T-type Ca2+ channels) channels .
•PHASE 0: THE RISING PHASE OR
DEPOLARIZATION:
•Opening of Long-lasting voltage-gated Ca
channels (L-type Ca2+ channels).
•Large influx of Ca.
•PHASE 3: THE FALLING PHASE OR
REPOLARIZATION:
•Opening of voltage-gated K channels
•Closing of L-type Ca channels.
•K Efflux.

50. AUTOMATICITY
 Chronotropism  depends on the slope of
pacemaker potential
 Modulation of HR by the ANS
 Discharge rate of the SA node normally exceeds
the other potentially automatic pacemaker sites
 Discharge rate of the SA node more sensitive
to the effects of ANS
 Normal or abnormal automaticity at other sites
in disease states  rates faster than the SA node
 control of the cardiac rhythm for one cycle or
more

51. EFFECT OF ANS
Sympathetics
• Incereases c AMP levels and
open Ca channels
• Steep slope for Phase 4
Parasympathetics
• c AMP levels decrease and
open additional K channels
and produce more
hyperpolarisation.
• Phase 4 takes longer to
reach the threshold voltage

52. ANTI ARRHYTHMIC DRUGS
Ia
↑ AP Duration
↑ ERP
↑ QT interval
Ib
↓ AP
↓ ERP
affects ischemic or
depolarized tissue
Ic
↑ ERP in AV node but
not in ventricular
tissue
II
↓ SA & AV nodal
activity
↓ cAMP and
↓ Ca2+ currents
↓ slope of phase 4
↑ PR interval
III
↑ AP Duration
↑ ERP
↑ QT interval
IV
↑ ERP
↑ PR interval
↓ Conduction velocity

53. THANK YOU