The Molecular Basis For Myocardial Contraction

Question 1

The myocardium: Main components

Answer 1

Contractile tissue,
Connective tissue,
Fibrous frame,
Specialised conduction system.

Question 2

What does the Cardiac Myocyte do? (1)

Answer 2

The pumping action of the heart depends on interactions between the contractile proteins in its muscular walls.

Question 3

What does the Cardiac Myocyte do? (2)

Answer 3

The interactions transform the chemical energy derived from ATP into the mechanical work that moves blood under pressure from the great veins into the pulmonary artery, and from the pulmonary veins into the aorta.

Question 4

What does the Cardiac Myocyte do? (3)

Answer 4

The contractile proteins are activated by a signalling process called excitation-contraction coupling.

Question 5

What does the Cardiac Myocyte do? (4)

Answer 5

Excitation-contraction coupling begins when the action potential depolarizes the cell and ends when ionized calcium (Ca2+) that appears within the cytosol binds to the Ca2+ receptor of the contractile apparatus.

Question 6

What does the Cardiac Myocyte do? (5)

Answer 6

Movement of Ca2+ into the cytosol is a passive (downhill) process mediated by Ca2+ channels.

Question 7

What does the Cardiac Myocyte do? (6)

Answer 7

The heart relaxes when ion exchangers and pumps transport Ca2+ uphill, out of the cytosol.

Question 8

The working myocardial cell

Answer 8

Filled with cross-striated myofibrils.

•Plasma membrane regulates excitation-contraction coupling and relaxation.

•Plasma membrane separates the cytosol from extra-cellular space and sarcoplasmic reticulum.

Question 9

Mitochondria

Answer 9

ATP, aerobic metabolism and oxidative phosphorylation.

Question 10

Myocardial metabolism

Answer 10

Relies on free fatty acids during aerobic metabolism (efficient energy production)

•During hypoxia, there is no FFA metabolism, thus anaerobic metabolism ensues.
This relies on metabolising glucose (anaerobically) producing energy sufficient to maintain the survival of the affected muscle without contraction.

Question 11

The Ultra-structure of the myocardial working cell (1)

Answer 11

Contractile proteins are arranged in a regular array of thick and thin filaments (The so called Myofibrils).

A band

I band

Z lines

Question 12

A band

Answer 12

the region of the sarcomere occupied by the thick filaments.

Question 13

I band

Answer 13

is occupied only by thin filaments that extend toward the centre of the sarcomere from the Z-lines. It also contains tropomyosin and the troponins.

Question 14

Z lines

Answer 14

Bisect each I band

Question 15

The Ultra-structure of the myocardial working cell (2)

The sacromere

Answer 15

The sarcomere: the functional unit of the contractile apparatus,

•The sarcomere is defined as the region between a pair of Z-lines,

•The sarcomere contains two half I-bands and one A-band.

Question 16

The Ultra-structure of the myocardial working cell (3)

The sarcoplasmic reticulum

Answer 16

The sarcoplasmic reticulum is a membrane network that surrounds the contractile proteins,

•The sarcoplasmic reticulum consists of the sarcotubular network at the centre of the sarcomere and the subsarcolemmal cisternae (which abut the T-tubules and the sarcolemma).

Question 17

The Ultra-structure of the myocardial working cell (4)

The transverse tubular system (T-tubule)

Answer 17

The transverse tubular system (T-tubule) is lined by a membrane that is continuous with the sarcolemma, so that the lumen of the T-tubules carries the extracellular space toward the center of the myocardial cell.

Question 18

Contraction

Answer 18

Sliding of actin over myosin by ATP hydrolysis through the action of ATPase in the head of the myosin molecule

•These heads form the crossbridges that interact with actin, after linkage between calcium and TnC, and deactivation of tropomyosin and TnI.

Question 19

TnC

Answer 19

Troponin C contains the binding sites for the Ca2+ that helps to initiate contraction.

Question 20

Troponin I

Answer 20

Troponin I inhibits the interaction of myosin with actin

Question 21

Myosin

Answer 21

• 2 heavy chains, also responsible for the dual heads

•4 light chains

•The heads are perpendicular on the thick filament at rest, and bend towards the centre of the sarcomere during contraction (row.)

Alpha Myosin and Beta Myosin

Question 22

Actin

Answer 22

•Globular protein.
•Double-stranded macromolecular helix (G).
•Both form the F actin.

Question 23

Tropomyosin

Answer 23

Elongated molecule, made of two helical peptide chains.
•It occupies each of the longitudinal grooves between the two actin strands.
•Regulates the interaction between the other three!

Question 24

Troponin

Answer 24

•I: with tropomyosin inhibit actin and myosin interaction.
•T: binds troponin complex to tropomyosin.
•C: high affinity calcium binding sites, signalling contraction.
•The latter bond, drives TnI away from Actin, allowing its interaction with myosin.

Question 25

The micro-anatomy of the contractile unit

Answer 25

Z, I, A and H zones,

•Myosin,

•Actin,

•Tropomyosin,

•Troponins,

•Titins,

•Calcium,

•ATP,

•Crossbridges.

Question 26

Control of the contractile cycle

Answer 26

Calcium ions

Troponin phosphorylation

Myosin ATPase

Question 27

Myosin

Answer 27

Location: Thick filament

Salient properties: Hydrolyses ATP, interacts with Actin

Question 28

Actin

Answer 28

Location: Thin filament

Salient Properties: Activates myosin ATP, interacts with myosin

Question 29

Tropomyosin

Answer 29

Location: Thin filament

Salient properties: Modulates actin-myosin interaction

Question 30

Troponin C

Answer 30

Location: Thin filament

Salient properties: Binds Ca2+

Question 31

Troponin I

Answer 31

Location: Thin filament

Salient properties: Inhibits actin-myosin interaction

Question 32

Troponin T

Answer 32

Location: Thin filament

Salient properties: Binds troponin complex to thin filament

Question 33

Summary

Answer 33

Contraction of the working cells of the myocardium involves interactions among six proteins: myosin of the thick filament, actin, tropomyosin, and the 3 components of troponin in the thin filament.

•These interactions are controlled by the downhill movement of Ca2+ into the cytosol (excitation-contraction coupling) and active Ca2+ transport out of the cytosol.

•All of these Ca2+ fluxes are highly regulated, which provides for the changes in cardiac muscle chemistry that give rise to changes in myocardial contractility.