The Molecular Basis For Myocardial Contraction Flashcards
The myocardium: Main components
Contractile tissue,
Connective tissue,
Fibrous frame,
Specialised conduction system.
What does the Cardiac Myocyte do? (1)
The pumping action of the heart depends on interactions between the contractile proteins in its muscular walls.
What does the Cardiac Myocyte do? (2)
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.
What does the Cardiac Myocyte do? (3)
The contractile proteins are activated by a signalling process called excitation-contraction coupling.
What does the Cardiac Myocyte do? (4)
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.
What does the Cardiac Myocyte do? (5)
Movement of Ca2+ into the cytosol is a passive (downhill) process mediated by Ca2+ channels.
What does the Cardiac Myocyte do? (6)
The heart relaxes when ion exchangers and pumps transport Ca2+ uphill, out of the cytosol.
The working myocardial cell
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.
Mitochondria
ATP, aerobic metabolism and oxidative phosphorylation.
Myocardial metabolism
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.
The Ultra-structure of the myocardial working cell (1)
Contractile proteins are arranged in a regular array of thick and thin filaments (The so called Myofibrils).
A band
I band
Z lines
A band
the region of the sarcomere occupied by the thick filaments.
I band
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.
Z lines
Bisect each I band
The Ultra-structure of the myocardial working cell (2)
The sacromere
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.
The Ultra-structure of the myocardial working cell (3)
The sarcoplasmic reticulum
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).
The Ultra-structure of the myocardial working cell (4)
The transverse tubular system (T-tubule)
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.
Contraction
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.
TnC
Troponin C contains the binding sites for the Ca2+ that helps to initiate contraction.
Troponin I
Troponin I inhibits the interaction of myosin with actin
Myosin
• 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
Actin
•Globular protein.
•Double-stranded macromolecular helix (G).
•Both form the F actin.
Tropomyosin
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!
Troponin
•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.
The micro-anatomy of the contractile unit
Z, I, A and H zones,
•Myosin,
•Actin,
•Tropomyosin,
•Troponins,
•Titins,
•Calcium,
•ATP,
•Crossbridges.
Control of the contractile cycle
Calcium ions
Troponin phosphorylation
Myosin ATPase
Myosin
Location: Thick filament
Salient properties: Hydrolyses ATP, interacts with Actin
Actin
Location: Thin filament
Salient Properties: Activates myosin ATP, interacts with myosin
Tropomyosin
Location: Thin filament
Salient properties: Modulates actin-myosin interaction
Troponin C
Location: Thin filament
Salient properties: Binds Ca2+
Troponin I
Location: Thin filament
Salient properties: Inhibits actin-myosin interaction
Troponin T
Location: Thin filament
Salient properties: Binds troponin complex to thin filament
Summary
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.
