The contraction of the Heart Reverend Dr. David C.M. Taylor School of Medicine [email protected]...

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The contraction of the Heart Reverend Dr. David C.M. Taylor School of Medicine [email protected] http://www.liv.ac.uk/~dcmt

Transcript of The contraction of the Heart Reverend Dr. David C.M. Taylor School of Medicine [email protected]...

Page 1: The contraction of the Heart Reverend Dr. David C.M. Taylor School of Medicine dcmt@liverpool.ac.uk dcmt.

The contraction of the Heart

Reverend Dr. David C.M. TaylorSchool of Medicine

[email protected]

http://www.liv.ac.uk/~dcmt

Page 2: The contraction of the Heart Reverend Dr. David C.M. Taylor School of Medicine dcmt@liverpool.ac.uk dcmt.

By the end of this lecture you should be able to discuss

The histology of cardiac muscle The role of myosin, actin, troponin and

tropomyosin The importance of calcium for contraction Starlings law Cellular and molecular events underlying cardiac

contraction and relaxation The role of Na+, K+ and Ca2+ in cardiac contractility

Learning outcomes

Page 3: The contraction of the Heart Reverend Dr. David C.M. Taylor School of Medicine dcmt@liverpool.ac.uk dcmt.

Structure of muscle

Chapter 13 p 147 in Preston and Wilson (2013)Chapter 9 p 437 in Naish and Court (2014)

Page 4: The contraction of the Heart Reverend Dr. David C.M. Taylor School of Medicine dcmt@liverpool.ac.uk dcmt.

Histology

Page 5: The contraction of the Heart Reverend Dr. David C.M. Taylor School of Medicine dcmt@liverpool.ac.uk dcmt.

The sarcomere

Chapter 12 p 136 in Preston and Wilson (2013)Chapter 9 p 437 in Naish and Court (2014)

Z line

Actinfilaments

Myosinfilaments

Page 6: The contraction of the Heart Reverend Dr. David C.M. Taylor School of Medicine dcmt@liverpool.ac.uk dcmt.

In more detail

myosin

actin

Troponin-tropomyosin complex

myosin binding site

Page 7: The contraction of the Heart Reverend Dr. David C.M. Taylor School of Medicine dcmt@liverpool.ac.uk dcmt.

In the presence of Calcium

• Tropomyosin shifts to expose the myosin binding site• Myosin binds to binding site• ATP is used to provide the energy to flex the myosin head• The muscle shortens

Page 8: The contraction of the Heart Reverend Dr. David C.M. Taylor School of Medicine dcmt@liverpool.ac.uk dcmt.

The muscle depolarises Excitation spreads over the sarcolemma and into the T-

tubules (there are fewer T-tubules than in skeletal muscle) L-type Ca2+ channels open (dihidropyridine receptors),

increasing sarcoplasmic Ca2+ levels Ca2+ induces Ca2+ release from the sarcoplasmic reticulum Ca2+ binds to tropomyosin• Tropomyosin shifts to expose the myosin binding site• Myosin binds to binding site• ATP is used to provide the energy to flex the myosin head• The muscle shortens

The order of events

Chapter 13 p 147 in Preston and Wilson (2013)Chapter 9 p 437 in Naish and Court (2014)

Page 9: The contraction of the Heart Reverend Dr. David C.M. Taylor School of Medicine dcmt@liverpool.ac.uk dcmt.

The heart does not remain contracted, but relaxes. This is caused by the activity of the SERCA

The SERCA is a Sarcoplasmic/Endoplasmic Reticulum Calcium ATPase

So energy is used to draw Ca2+ back into the sarcoplasmic reticulum.

And the myosin is released from the actin filaments…

Then

Chapter 13 p 150 in Preston and Wilson (2013)Chapter 9 p 440 in Naish and Court (2014)

Page 10: The contraction of the Heart Reverend Dr. David C.M. Taylor School of Medicine dcmt@liverpool.ac.uk dcmt.

The principles are exactly the same as for neurones

But the action potentials last much longer And Ca2+ ions are more important

Na+ and K+ regulate the rate of contraction Ca2+ regulates the force of contraction The more Ca2+, for whatever reason, the greater

the force of contraction All three are regulated by the autonomic nervous

system

Na+, K+ and Ca2+

Page 11: The contraction of the Heart Reverend Dr. David C.M. Taylor School of Medicine dcmt@liverpool.ac.uk dcmt.

The action potential (revision)

-70 mV-55mV

+40mV Fully permeable to Na+(+40mV)

Fully permeable to K+ (-90mV)

1mS

Resting membrane potential(-70mV)

Page 12: The contraction of the Heart Reverend Dr. David C.M. Taylor School of Medicine dcmt@liverpool.ac.uk dcmt.

The action potential (revision)

-70 mV-55mV

+40mV

VANC open

VANC close Fully

permeable to Na+(+40mV)

Fully permeable to K+ (-90mV)

1mS

stimulus

Resting membrane potential(-70mV)

gNa+

gK+

Page 13: The contraction of the Heart Reverend Dr. David C.M. Taylor School of Medicine dcmt@liverpool.ac.uk dcmt.

Pacemaker activity

The rhythm of the pump is provided by the pacemaker activity of some specialized muscle cells in the wall of the right atrium - the sinoatrial node

There is a steady inward current of both Na+ and Ca2+

Which causes a gradual depolarisation

0

mV

-70

0 mS 300

Page 14: The contraction of the Heart Reverend Dr. David C.M. Taylor School of Medicine dcmt@liverpool.ac.uk dcmt.

Factors affecting stroke volume

Preload Afterload

Contractility

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Preload

increased end-diastolic volume stretches the heart

cardiac muscles stretch and contract more forcefully Frank-Starling Law of

the heart 40 60 80 100 120 140 160

Percentage sarcomere length (100% = 2.2 µm)

100

80

60

40

20T

ensi

on d

evel

oped

%

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Starling’s Law

40 60 80 100 120 140 160Percentage sarcomere length (100% = 2.2 m)

100

80

60

40

20

Ten

sion

dev

elop

ed %

1.8 m2.2 m

3.8 m