ELECTRICAL PROPERTIES OF THE HEART Sandor Gyorke, Ph.D. Office: DHLRI 507 Telephone: 292-3969 Email: [email protected].

ELECTRICAL PROPERTIES OF THE HEART

Sandor Gyorke, Ph.D.Office: DHLRI 507

Telephone: 292-3969Email: [email protected]

Learning Objectives• Differentiate pacemaker cells from myocardial cells by

action potential characteristics and ion transport during depolarization and repolarization and response to sympathetic and parasympathetic stimulation.

• Describe the sequence of activation of the heart and relate to the components of the electrocardiogram.

• Identify the components of the conduction system of the heart.

At the end of this module, you will learn to

Learning Resources

Pathophysiology of Heart Disease. Fifth Edition, Ed. L.S. Lilly, Lippincott Williams & Wilkins, Baltimore, MD, 2011 (pp. 12-23; 75-112)

D.E. Mohrman & L.J. Heller. Cardiovascular Physiology, 8th edition, McGraw-Hill, New York 2014.

Topics• Membrane excitability • Cardiac resting potential • Cardiac action potentials• Heart rhythm • The sequence of electrical activation of the heart• Cardiac electrocardiogram (ECG)

Electrical excitation

Contraction

• Cardiac myocytes are electrically excitable cellscapable of generating and conducting action potentials

• Disturbances in normal periodic electrical activity result in cardiac arrhythmia.

• All electrical phenomena in the heart rely on movement of ions across membranes

• The heart is composed of cardiac muscle cells, cardiomyocytes.

• There are two types of cardiac cells: “working” cardiomyocytes with fast action potential (in ventricles and atria) and cardiac pacemaker cells with slow action potential.

Introduction

Internal External[Na+] 15 mM 150 mM[K+] 150 mM 5 mM[Cl-] 5 mM 120 mM [Ca2+] 10-7 M 2 mM

Ca2+Na+

K+

Na+ Ca2+Ca2+

Na+

sarcolemmaChannels

Pumps

Sarcolemma:• Phospholipid bilayer• Pumps/transporters • Ion channels

K+

Transport and Distribution of Ions in Cardiac Myocytes

Background (IKr) Responsible for generation Kir2.1K+ current of the resting potential

Diastolic pacemaker (If) Responsible for spontaneous HCN2 current depolarization in pacemaker cells

Fast Depolarizing (INa) Initial depolarization SCN5A Na+ current of cardiac action potentials

Delayed repolarizing (IK) Helps to terminate action HERG K+ current potential plateau

Slow Ca2+ current (ICa) Important for plateau phase α 1C of action potential

Current Abbreviation Role Gene

Major Cardiac Voltage-gated Membrane Currents

PP

ATP ADP

Na+

K+

K+

Na+

2 K+

3 Na+ATPase

3 Na+

2 K+

• 3Na+/2K+• 150 cycles/sec• Maintenance of Na+ and K+

gradients requires ~20% of total ATP produced by the cell

in/out: 15/150 mM

in/out: 150/5 mM

inside

outside

Na - K ATPase (The Sodium-Potassium ATPase pump)

[K+]i

(150 mM) [K+]o

(5 mM)

K+

+ -+ -

+ -

K+

Na+

V

VM = -90 mV

Polarized state that makes possible generation of electrical signals

IKr

12

3

1) The Na/K-ATPase generates a K+ gradient by utilizing energy stored in ATP;

2) K+ flows out of the cell through K+ channels leaving behind anions; 3) K+ moves back attracted by the negative charge at the inner membrane face;

The Resting Membrane Potential

• Basis for signal-carrying ability of cardiac myocytes

• Allows large areas of the heart to contract almost simultaneously

• Drives cardiac rhythm

• Two main types: fast (non-pacemaker) and slow (pacemaker)

The Cardiac Action Potential

Mem

bran

e po

tent

ial

(m

V)

-100

0

+50

-100

0

+50

Nerve and skeletal muscle

Cardiac myocyte

• Can be recorded throughout most of the heart except the pacemaker and conduction regions

• The cardiac AP is much longer than the nerve and skeletal AP and is composed of a fast upstroke and a slow plateau

Upstroke Plateau

The Fast Action Potential

-100

0

+50Membrane potential (mV)

1 (Initial Repolarization)

2 (Plateau) 3

(Repolarization)

4 (Resting Potential)

4

gNa

gCa

gK

0 (Depolarization)

ION

CO

ND

UC

TAN

CE

S INa

ICa

IK IKrIKr

Phases of the Fast Action Potential

-100

0



2 (Plateau) 3

(Repolarization)


4

gNa

gCa

gK

0 (Depolarization)

ION

CO

ND

UC

TAN

CE

S INa

ICa

IK IKrIKr

Phase 4 (Resting Potential )

Outside

Inside

K+

Outside

Inside

OutsideIKr IK

Inside

K+


-100

0



2 (Plateau) 3

(Repolarization)


4

gNa

gCa

gK

0 (Depolarization)

ION

CO

ND

UC

TAN

CE

S INa

ICa

IK IKrIKr

Phase 0 (Depolarization )

Outside

Inside

Outside

Inside

OutsideIKr IK

Inside

Na+


-100

0



2 (Plateau) 3

(Repolarization)


4

gNa

gCa

gK

0 (Depolarization)

ION

CO

ND

UC

TAN

CE

S INa

ICa

IK IKrIKr

Phase 0 (Depolarization )

Outside

Inside

Outside

Inside

OutsideIKr IK

Inside

Na+

Na+


-100

0



2 (Plateau) 3

(Repolarization)


4

gNa

gCa

gK

0 (Depolarization)

ION

CO

ND

UC

TAN

CE

S INa

ICa

IK IKrIKr

Phase 1 (Initial Repolarization )

Outside

Inside

Outside

Inside

OutsideIKr IK

Inside


-100

0



2 (Plateau) 3

(Repolarization)


4

gNa

gCa

gK

0 (Depolarization)

ION

CO

ND

UC

TAN

CE

S INa

ICa

IK IKrIKr

Phase 2 (Plateau)

Outside

Inside

K+

Outside

Inside

OutsideIKr IK

Inside

Ca2+


-100

0



2 (Plateau) 3

(Repolarization)


4

gNa

gCa

gK

0 (Depolarization)

ION

CO

ND

UC

TAN

CE

S INa

ICa

IK IKrIKr

Phase 3 (Repolarization)

Outside

Inside

K+

Outside

Inside

OutsideIKr IK

InsideK+


Action Potential Contraction

Absoluterefractory period

Relative refractory period

Skeletal muscle fiber Cardiac myocyte

refractory period

• Inability to respond to further stimulation • Allows the ventricles sufficient time to empty their

content and refill before the next cardiac contraction

Refractory Periods

Me

mbr

an

e p

ote

ntia

l

(m

V)

-70

0

gNa

gCa

gK

ION

CO

ND

UC

TAN

CE

S If

ICa

IK

SA Node

AV Node

RepolarizationDepolarization

Pacemaker potential

4

0 3

4Threshold

The Pacemaker Action Potential

• Conducts both K+ and Na+

• Opens (inward current) at hyperpolarized potentials

• cAMP accelerates activation kinetics

• Responsible for initial phase of spontaneous depolarization in the nodal tissue

Properties of If

Vagal Symp

50Intrinsic Rate(60-100 bpm)

200 bpm

+ Norepinephrine+ Acetylcholine

Threshold

Positive chronotropic effect

Negativechronotropic effect

ACH NE

ACH

Vagal Symp

SA Node

Modulation of Pacemaker Activity

Gsb-R

b-Agonist

cAMPP

Ca2+ Channel

AC

ATP

ATP ADPCR

PKA

C

P

Na+/K+ Channel

Molecular Mechanisms of Positive Chronotropic Effects of β-AGONISTS

Gi

AchR

cAMP

Ca2+Channel

AC

ATP

Ach

P P

Na+/K+ Channel

Molecular Mechanisms of Negative Chronotropic Effects of Acetylcholine

• Electrical coupling of myocytes via gap junctions

• Cardiac conduction system

Conduction of Action Potentials Through the Heart

Gap junctions

Connexons

- - - - - - + + + + + + ++ + + + + + - - - - - -

• Large-conductance pores permeable for ions and small molecules

• Consist of two sets of six subunits (connexons)

• Responsible for electrical coupling of myocytes

Propagation of the Action Potential Along Cardiac Cells

Gap junctions

- - - - - - - - - - - - - - - + + + + + + + + + + + + + + + + + + + + + - - - - - -

Connexons

• Large-conductance pores permeable for ions and small molecules

• Consist of two sets of six subunits (connexons)

• Responsible for electrical coupling of myocytes

Propagation of the Action Potential Along Cardiac Cells

SA Node

AV Node

Purkinjefibers

RV LV

LARA

Bundle of His

Left Bundle Branch

Right Bundle Branch

The Cardiac Conduction System

SA Node

AV Node


SA Node

AV Node

Conduction velocity ~0.5-1 m/sec Atrium activation occurs within ~100 ms nearly synchronously


AV Node Conduction velocity slows to ~0.2 m/sec This permits atrial relaxation occur before ventricularContraction begins


Bundle of His

Left Bundle Branch

Right Bundle Branch

Conduction velocity is fast ~4 m/sec so the entire ventricle is activated simultaneously


Purkinjefibers

Conduction velocity is fast ~4 m/sec so the entire ventricle is activated nearly simultaneously


The Electrocardiogram

ECG is a noninvasive recording of electrical activity of the working heart

A most commonly used diagnostic tool that provides information on:

• Anatomical orientation of the heart• Relative sizes of chambers• Disturbances of rhythm and conduction• Extent, location of ischemic damage

Represents the sum of action potentials occurring simultaneously in many individual cells

- - - - - - - - -+ + + + + + + + +

- - - - - - - - -+ + + + + + + + +

- - - - - - - - -+ + + + + + + + +

- - - - - - - - -+ + + + + + + + +

- - - - - - - - -+ + + + + + + + + - - - - - - - - -

+ + + + + + + + +

Depolarization- - - - - - - - -+ + + + + + + + +

- - - - - - - - -+ + + + + + + + +

(+) (-)

Extracellular Recording of Depolarization and Repolarization in a Strip of Cardiac Muscle

RA(-)

Polarity: When LL becomes positive with respect to RA an upward deflection is recorded

+ +

+

+- ---

+

-

LL (+)

ECG Recording as a Wave of Depolarization Along the Longitudinal Axis of Heart

P

Q

R

S

T

PR interval<0.2 s

QT interval~0.4 s

P w

ave

PR

se

gm

en

t

ST

se

gm

en

t

T w

ave

QR

S c

om

ple

x


P wave – atrial depolarization

QRS complex – ventricular depolarization

T wave – ventricular repolarization

PR interval – passage through the AV conduction system

QT interval – period of electrical systole

RA(-)

LL (+)

Components of a Typical ECG Recording

P

Q

R

S

T

PR interval<0.2 s

QT interval~0.4 s

P w

ave

PR

se

gm

en

t

ST

se

gm

en

t

T w

ave

QR

S c

om

ple

x

P wave – atrial depolarization

QRS complex – ventricular depolarization

T wave – ventricular repolarization

PR interval – passage through the AV conduction system

QT interval – period of electrical systole

RA(-)

LL (+)


Components of a Typical ECG Recording

SA Node

AV Node

P QRS T

+

_

The Sequence of Activation of Heart in Relation to ECG

SA Node

AV Node

P QRS T

Atrial depolarization

+

_


SA Node

AV Node

P QRS T

Depolarization of theintraventricular septum

+

_


SA Node

AV Node

P QRS T

Depolarization of large part of ventricular myocardium

+

_


SA Node

AV Node

P QRS T

Depolarization of a small portion of ventricular myocardiumnear the base

+

_


SA Node

AV Node

P QRS T

Depolarization of whole ventricular myocardium

+

_


SA Node

AV Node

P QRS T

Ventricular repolarization (progresses from the apex to the base)

+

_


Summary• For contraction to occur cardiac cells rely on action potentials (APs).

The rapid upstroke of APs of atrial and ventricular cells is due to a Na+ current (INa). The prolonged plateau phase of these APs is due to a Ca2+ current (ICa), repolarization to potassium currents (IK), and the resting potential is due to another potassium current called IK1.

• APs in pacemaker cells rely on ICa for their upstroke, IK to repolarize, and on a funny current (If) to provide the diastolic pacemaker potential which slowly depolarizes the membrane between APs.

• Normally APs are generated in the SA node. The impulse propagates from the SA node to both atria and to the AV node, where a delay occurs. The impulse then passes into the bundles of His, right and left bundle branches, Purkinje fibers, and working ventricular myocytes.

• The electrocardiogram (ECG) is recorded from the surface of the body and traces the conduction of the cardiac impulse through the heart.

Electrical Properties of the Heart Quiz

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ELECTRICAL PROPERTIES OF THE HEART Sandor Gyorke, Ph.D. Office: DHLRI 507 Telephone: 292-3969 Email: [email protected].

Documents

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