Cardiac electrical activity

Understanding the electrical activity of the heart is important because:

The electrical activity precedes and induces the mechanical activity.

The path, timing, and sequencing of the electrical activity is a large

determinant of the effectiveness of the mechanical activity.

Abnormalities in electrical activity are common causes of disability & death

Measuring the electrical activity (ECG) aids in diagnosis of cardiac problems.

Electrical activity in biological systems is produced by diffusion of ions across membranes

Ions diffuse across cell membranes through specific water-filled channels driven by

the electric & concentration gradients across the membrane.

In cardiac myocytes the resting membrane potential is produced mostly by diffusion

of K+ down it’s concentration gradient out of the cell.

Action potentials in nerve & muscle are due to rapid diffusion of Na+ into the cell

down it’s electrochemical gradient. (Exception: action potentials in the SA and AV

nodes are due to diffusion of Ca++ through L-type Ca++ channels.)

Channels of interest in the cardiovascular system are:

Voltage-gated: open with a change in membrane potential.

Ligand gated: open in response to a hormone or intracellular signal.

Stretch activated: open in response to stretch of a myocyte

Equilibrium potential (or Nernst potential):

If the membrane potential = the equilibrium potential for an ion, the rates of

passive diffusion of the ion into and out of the cell are equal.

out

inK K

KLog5.61E

The equilibrium potential for an ion is the membrane potential at which the effects of electrical and concentration gradients on diffusion of the ion balance each other.

K+ = 4 mEq/L

A-

K+ = 135 mEq/L

------

++++++

K+ = 4 mEq/L

Electrical gradient: Negative resting membrane potential drives K+ into cell.

Concentration gradient: Higher cell [K+] drives K+ out of cell.

A - = intracellular anionic proteins & organic phosphates balance positive charge on K+.

Equilibrium potential (Nernst potential) for Na+, K+ & Ca++

Cardiac myocyte resting Membrane Potential = - 90 mV

mV94L/mEq4

L/mEq135Log5.61E

K

I/O = 33.75

K+

135

4

inside

outside

O/I = 20,000

mV132L/mEq2

L/mEq0001.Log75.30E

Ca

Ca++

0.0001

2

inside

outside

mV70L/mEq145

L/mEq10Log5.61E

Na

O/I = 14.5

Na+

10

145

inside

outside

Equilibrium potential compared to resting membrane potential (RMP)

[inside]/[outside]Equilibrium

potential, mVRMP, mV

EK+ 135/4 - 94 - 90Concentration & electrical forces are opposite; concentration > electrical

ECl- 4/110 - 70 - 90concentration & electrical forces are opposite; electrical > concentration

ENa+ 10/145 + 70 - 90Concentration & electrical forces act in same directionECa++ .0001/2 + 132 - 90

Membrane pumps and potentials in a ventricular myocyte

[Na+] = 10 mEq/L

[K+] = 135 mEq/L

Sarcoplasmic reticulum:Ca++ storeCa++ released during excitationCa++ taken up during relaxation by Ca++ ATPase in SR (SERCA)

Ca++ ATPaseCa++

[Na+] = 145 mEq/L

[K+] = 4 mEq/L

Voltage-gated L type Ca++ channel

RMP = -90 mV

Na+ Na+

Ca++ Ca++

Ca++ATPase

Ca++ Ca++

3 Na+ 3 Na+

2 K+ 2 K+

ATPase

Ca++

Ca++

Na+

Na+

K+

K+

passive

active

Na + Ca++

exchange

The resting membrane potential is primarily determined by diffusion of K+

Changing extracellular [K+] changes the concentration gradient for diffusion of K+ out of the cell and the equilibrium potential (EK

+, Nernst potential) for K+.

Parallel changes in EK and the resting membrane potential mean that diffusion of K+ is the main determinant of the resting membrane potential.

[K+in] = 135 mEq/LExtracellular [K+], mEq/L

Tra

nsm

embr

ane

pot

entia

l, m

V

Resting membrane potential

-150

-100

-50

0

5 10 20 30 501 2 3

Equilibrium potential for K+

Changing extracellular [K+] changes the concentration gradient for diffusion of K+ out of the cell

Normal

Hyperkalemia: gradient for diffusion of K+ is decreased.

K+ = 4 mEq/L

K+ = 135 mEq/L----

++++ RMP = - 90 mV

K+ = 7 mEq/L

K+ = 135 mEq/L----

++++ RMP = - 75 mV

Hypokalemia: gradient for diffusion of K+ is increased.

K+ = 2 mEq/L

K+ = 135 mEq/L----

++++ RMP = - 95 mV

Effects of acute and chronic hyperkalemia

Depolarization inactivates fast Na+ channels

excitability

cardiac conduction velocity

Chronic

Skeletal muscle weakness

hyperkalemia depolarizes RMP

RMP approaches threshold

excitability

Acute

“Symptoms of hyperkalemia … do not become manifest until the plasma potassium concentration exceeds 7.0 mEq/L , unless the rise in potassium concentration has been very rapid.” (B.D. Rose, UpToDate 2008).

Effects of acute and chronic hypokalemia

Hyperpolarization activates some fast Na+ channels

excitability

cardiac arrhythmias

Chronic

Skeletal Muscle weakness

Hypokalemia hyperpolarizes RMP

RMP becomes more negative relative to threshold

excitability

Acute

Symptoms usually occur only if plasma K+ is below 2.5 to 3 mEq/L

Phases of a ventricular myocyte action potential (0, 1, 2, 3, 4)

- 90 mV

zero mV

milliseconds

0 100 200 300

ARPRRP

0

2

3

4

1

ARP = absolute refractory periodRRP = relative refractory period

Ion channels in the cardiac myocyte action potential

- 90 mV

- 70 mV upshoot:threshold for fast Na+ channel activation

- 55 mV: fast Na+ channel inactivation

- 40 mV: L-typeCa++ channel activation

Plateau: L Type Ca + + channels open,Some K+ channels close

Repolarization:Ca + + channels close,K+ channels open

zero mV

gNa+

gK+

gCa++

g = conductance = 1/resistance

0 3

4

1 2

Summary of ionic currents in cardiac myocyte action potential

Phase Ionic current

0 Upshoot Influx of Na+

1 Transient repolarization Transient efflux of K+

2 Plateau Influx of Ca++; decreased efflux of K+

3 Repolarization Decreased influx of Ca++; increased efflux of K+

4 Rest Resting potential set by efflux of K+

0

3

4

1 2

Influx: flow into cell.Efflux: flow out of cell

The upshoot of the AP is determined by diffusion of Na+ into the cell

-100

-80

-60

-40

-20

0

20

40

Extracellular [Na+]

Po

ten

tial,

mV

Resting membrane potential

Upshoot of action potential

15 30 50 150

Ventricular myocyte action potential

As ECF [Na+] decreases (x axis) the magnitude (height) of the upshoot decreases (y axis) because the Na+ concentration gradient across the cell membrane decreases.

All or none law and force of contraction

Skeletal Muscle Cardiac Muscle

Action potential obeys “all or none” rule Action potential obeys “all or none” rule

Single APs consistently release the same amount of Ca++ from the SR

The amount of Ca++ released from the SR depends on the level of adrenergic stimulation.

Increased force of contraction occurs by tetany or by recruitment of more motor units

Increased force of contraction occurs by adrenergic stimulation resulting in more Ca++ interacting with the contractile mechanism

Extracellular Ca++ is not needed for contraction

Extracellular Ca++ is necessary for contraction (Ca++-Induced Ca++ Release)

SR = sarcoplasmic reticulum

Pacemaker cells in the sino-atrial node set the normal heart rate

The pacemaker potential is a spontaneously depolarizing membrane potential carried by a ”funny” Na+ current, If. This current is called “funny” because the responsible

channels open as the cell membrane repolarizes (becomes more negative) past –50 mV. Other Na+ channels open when the membrane depolarizes.

The upshoot of the action potential is a calcium current, ICa++. due to opening of L-type

Ca++ channels.

Repolarization is due to an outward K+ current, IK+ due to opening of K+ channels.

0

-20

-60

-40

-80

Threshold – 55 mV

outward

inward

ICa++

IK+

If

Ionic currents

Path of excitation in the heart

Sino-atrial node originates action potentials

Atrial myocytes

Atrioventricular node

Bundle of His

Right & left bundle branches

Ventricular myocytes

Purkinje fibers

The heart is a syncytium.

Depolarization (inward Na+ current) spreads from conducting tissue to myocytes & between myocytes via gap junctions.

Gap junctions are located at the ends of myocytes and conduct current longitudinally.

The velocity of conduction of APs is greatest in the Purkinje fibers.

The AV node is the only pathway for conduction between atria & ventricles

Conduction is delayed in the AV node allowing optimal ventricular filling during atrial contraction.

Conduction velocity

Velocity of conduction of action potentials in cardiac myocytes and Purkinje fibers is directly proportional to:

1) Fiber diameter (greatest in Purkinje fibers).

2)The magnitude of the upshoot of the AP.

3) Rate of rise of the AP in phase 0 (increase slope of phase 0).

Magnitude of AP Rate of rise of AP

Local current (depolarization)

Conduction velocity

Both an increase in the magnitude of the action potential and a more rapid rate of rise of the AP in phase 0 cause greater depolarization of the cell membrane locally, opening more fast Na+ channels and increasing conduction,.

Conduction velocity, plasma [K+] & ischemia

Depolarization from any cause decreases conduction velocity in Purkinje fibers & myocytes.

Conduction velocity in hyperkalemia leads to abnormal conduction & disturbances in cardiac rhythm.

ischemia

Activity of Na+. K+ ATPase

Leak of K+ from cells

extracellular [K+]

Gradual depolarization

Inactivation of some Na+ channels

Local currents

Conduction velocity

K+ concentration gradient.

Magnitude of AP Rate of rise of AP

potential driving Na+ entry

Automaticity & latent pacemakers

In addition to the SA node, the AV node & Purkinje fibers may show pacemaker potentials.

The heart rate is set by the pacemaker that is depolarizing at the fastest rate, normally the SA node.

Damage or blockade of the SA node will allow slower pacemakers to take over & results in bradycardia (decreased HR).

Pacemaker Intrinsic rate

SA node 60- 100 B/min

AV node & bundle of His 50- 60 B/min

Purkinje fibers 30 – 40 B/min