Layers of The Heart

# Sheet 2 Subject Physiology Done by Corrected by Doctor Layers of The Heart 1- Pericardium: The heart is enclosed within the pericardium fixing it in the mediastinum. It is a double-walled sac containing the heart and the roots of the great vessels. The pericardial sac has two layers: 1- The fibrous layer: the most superficial layer which acts to protect the heart and anchors it. 2- The serous layer: functions in lubricating the heart to prevent friction during heart activity. It is divided into two layers: a- Parietal layer, which is fused to the fibrous layer. b- Visceral layer (epicardium), which is in contact with the myocardium.  In between the parietal and visceral layers, there is a potential space called the pericardial cavity, which contains the pericardial fluid which acts as a shock absorber. Abnormal accumulation of fluid in the pericardial cavity is a pathological case called ‘pericardium effusion’. A pericardial effusion with enough pressure to adversely affect heart function is called cardiac tamponade. In this case, the fluid is drained through a needle to restore normal conditions temporarily until treating the underlying cause. 1|Page 2- Myocardium: It is the middle layer of the heart wall. It is composed of cardiac muscle fibers, which enable heart contractions. The myocardium is the thickest layer of the heart wall. 3- Endocardium: It is the thin inner layer of the heart wall. This layer lines the inner heart chambers, covers heart valves, and is continuous with the endothelium of large blood vessels. It is made up of endothelial cells that produce substances regulating the myocardial function affecting contractility and blood flow. For example, Nitric Oxide (NO) is an endothelium-derived relaxing factor. Cardiac Muscle: Myocardium The myocardium is an involuntary, striated muscle, and located between the epicardium (visceral pericardium) and endocardium. It differs from the skeletal muscles in: 1- The skeletal cells are spindle in shape, while the myocardial cells are rectangular in shape. 2- Myocardium has a syncytium structure ‘discussed later’. 3- Skeletal muscles do not have any cell-cell junctions, whereas cardiac muscle cells contain gap junctions and desmosomes at the intercalated discs. ➔ Desmosomes stop separation during contraction, while gap junctions transmit action potentials. 4- In contrast to skeletal muscle, the myocardium cells are rich in mitochondria but low in nuclei. In the cardiac muscle, there is a lot of oxidative phosphorylation needed to provide energy which explains the large amounts of mitochondria. 5- Poorly developed sarcoplasmic reticulum in the cardiac muscle compared to the skeletal muscle indicates that skeletal muscle stores enough calcium, while in cardiac muscle it is not enough and accordingly it takes calcium from the extracellular fluid. 2|Page 6- Cardiac muscle contains one T-tubule per sarcomere at the Z-line. Skeletal muscles contain 2 T-tubules. 7- Sarcomeres in the cardiac muscle are wider and shorter compared to the skeletal muscle. 8- There is no tetany in the cardiac muscle ‘discussed later’. 9- Fatty acids are the main source of energy for contraction in the myocardium. Gap Junctions - Gap junctions are hexagonal proteins that are voltage-sensitive. They allow action potentials to spread between cardiac cells by permitting the passage of ions between cells. - They are called ‘electrical couplers’ as they provide low electrical resistance areas between the myocardium cells, thereby increasing their electrical coupling to adjacent cells allowing coordinated contractility. - The loss of the coordinated contraction of the ventricular myocardium causes Ventricular Fibrillation, which requires defibrillation through a DC shock (directcurrent shock). Cardiac Syncytium - It is a network of cardiac cells connected to each other by intercalated discs that enable the rapid transmission of electrical impulses, enabling the syncytium to act in a coordinated contraction of the myocardium as a single unit. - The heart contains 2 syncytia: Atrial and Ventricular Syncytium. 3|Page Action Potential in The Cardiac Muscle - As we took before, in skeletal muscle the resting membrane potential is -70 mV. Depolarization takes place caused by Na+ influx, followed by repolarization caused by K+ efflux. As for cardiac muscle, the resting membrane potential is more negative, around -90 mV. The action potential has 5 phases: Phase 0 (depolarization): fast Na+ channels open When the cardiac cell is stimulated, voltage-gated sodium channels (fast sodium channels) open and permit sodium to rapidly flow into the cell depolarizing it.  High conductance of Na+ with decreased permeability of K+. Phase 1 (initial repolarization): fast Na+ channels close Na+ channels close, the cell begins to repolarize, and K+ leave the cells through open K+ channels. Phase 2 (plateau): Ca+2 channels open and K+ channels close: After the brief initial repolarization, decreased K+ permeability (decreased efflux) and increased Ca+2 permeability (increased influx) causes the action potential to plateau. Note: Ca+2 ions are important for the plateau. Phase 3 (rapid repolarization): Ca+2 channels close and K+ channels open The closure of Ca+2 channels and increased K+ permeability, permitting K+ to rapidly exit the cell, end the plateau and returns the cell membrane potential to its resting level. Phase 4 (resting membrane potential): averages about -90 mV. 4|Page Ion gates conformational changes during action potential: - The 3 typical voltage-gated channels in an action potential are: 1- M gate (activation gate): controls Na+ channel opening (extracellular gate). 2- H gate (inactivation gate): controls Na+ channel closing (intracellular gate). 3- N gate: controls K+ channel opening. - The M gate acts very fast while the H gate is slow. As the membrane potential becomes less negative, the M gate opens and the H gate closes after a while; since its slower. - This image is a simple presentation of the ion channels during 4 stages of action potential: At rest: Na+ channel is closed but capable of opening. Depolarization: Na+ channel is open. Repolarization: Na+ channel is closed and not capable of opening. Hyperpolarization 5|Page The refractory period in cardiac muscle: The cardiac muscle has a long refractory period given the presence of a plateau. During this period, the membrane is refractory (resistant) to further stimulation until the contraction is over. Notice the length of the refractory period in the picture and how it ends near complete relaxation: In skeletal muscles, the refractory period ends earlier permitting ‘Tetanus’. The refractory period in the cardiac muscle is longer than in the skeletal muscle preventing tetanus. This is important to: 1- Give time to the heart to relax after each contraction preventing fatigue. 2- Allow the heart chambers to fill during diastole before the next contraction. 6|Page Mechanism of Cardiac Muscle Contraction - The mechanism by which calcium concentrations within the cytosol rise differ between skeletal and cardiac muscle. - In cardiac muscle, the action potential comprises an inward flow of both Na+ and Ca+2 ions. The flow of Na+ is rapid but very short-lived, while the flow of Ca+2 is sustained and gives the plateau phase of cardiac muscle action potentials. - The small flow of extracellular Ca+2 triggers a larger release of Ca+2 from the sarcoplasmic reticulum in a phenomenon known as ‘calcium-induced calcium release’. - In contrast, in skeletal muscle, minimal Ca+2 flows from the endoplasmic reticulum only. This difference can be attributed to the fact that cardiac muscle fibers require high concentrations of Ca+2 in order to contract, while skeletal muscle fibers will contract without extracellular Ca+2. During Contraction: - During contraction of a cardiac muscle cell, the protein myofilaments bind forming crossbridges to slide over each other allowing contraction. There are thick 'myosin' and thin 'actin' myofilaments: a- Troponin is a complex attached to the protein tropomyosin which are both components of the thin actin filament. In a relaxed muscle, tropomyosin blocks the attachment site for myosin blocking crossbridges formation, thus preventing contraction. b- When the muscle cell is stimulated by an action potential to contract, Ca+2 channels open in the sarcoplasmic membrane and release Ca+2 into the sarcoplasm. Calcium ions attach to troponin which moves tropomyosin away from the myosin-binding sites on actin exposing them. Myosin, in the thick filament, can then bind to actin, pulling the thick filaments along the thin filaments through ‘power strokes’ using ATP, and contraction of the muscle begins. 7|Page During Relaxation: - Relaxation occurs when calcium is pumped back to its storage site by three mechanisms: 1- Ca+2 ATPases (Ca+2 pumps on the sarcoplasmic reticulum membrane): They are intracellular pumps located in the sarcoplasmic or endoplasmic reticula of muscle cells. They translocate Ca+2 from the cytosol to the sarcoplasmic reticulum lumen, sequestrating calcium ions. They are regulated by a protein called phospholamban (located on the sarcoplasmic reticulum membrane). a- Phospholamban in the dephosphorylated state is an inhibitor of Ca+2 ATPases. b- Phospholamban in the phosphorylated by ATP activates Ca+2 ATPase and enhances its efficiency in moving Ca+2 to SR inducing contraction. Phospholamban can get phosphorylated through: - Protein Kinase A: cAMP dependent protein kinase. - Protein Kinase B: Ca+2 - Calmodulin dependent protein kinase. - Protein Kinase C: Ca+2- phospholipid dependent protein kinase.  The overall effect of phospholamban is to sequester calcium ions into the SR by activating Ca+2 ATPase; to decrease contractility and the rate of muscle relaxation, thereby decreasing stroke volume and heart rate, respectively. 2- Na+ / Ca+2 exchanger (on the sarcolemma): It exchanges one Ca+2 ion for three Na+ ions reducing intracellular Ca+2 concentration. It is an electrogenic pump which means that it leads to the accumulation of charges across the plasma membrane “sarcolemma”. Some drugs block Na+ / Ca+2 exchanger, producing an inotropic effect, they are called positive inotropic drugs; which are agents that increase the strength of muscular contraction. Note: Na+ / Ca+2 exchangers can work in both ways; either sodium in-calcium out, or calcium in-sodium out. 8|Page 3- ATP-dependent Ca+2 pumps (on the sarcolemma): These pumps act to maintain a low concentration of free cytosolic Ca2+. Remember: a- Affinity is related to Km; it is the binding strength between the substrate and the enzyme. b- Capacity is how many molecules can the enzyme act on in a certain amount of time. Ca+2 pumps in the sarcolemma have high affinity and low capacity. Thus, they are capable of working at low concentrations of calcium but does not transport too much Ca+2. On the other hand, Na+ / Ca+2 exchangers in the sarcolemma have low affinity and high capacity. Note: if the three mechanisms are not enough to reduce Ca+2 concentration in the cardiac muscle and cause relaxation, which is a pathological condition, Na+ / Ca+2 exchanger in the membrane of the mitochondria will start functioning to reduce Ca+2 concentration. 9|Page