cvs-2.pdf

Cardiovascular system Lec.2 By Dr. Zainab H.H Alamily 1. Sinoatrial (SA) node is normally the pacemaker of the heart. has an unstable resting potential. exhibits phase 4 depolarization, or automaticity. The AV node and the His-Purkinje systems are latent pacemakers that may exhibi...

Cardiovascular system Lec.2 By Dr. Zainab H.H Alamily 1. Sinoatrial (SA) node is normally the pacemaker of the heart. has an unstable resting potential. exhibits phase 4 depolarization, or automaticity. The AV node and the His-Purkinje systems are latent pacemakers that may exhibit automaticity and override the SA node if it is suppressed. The intrinsic rate of depolarization (and heart rate) is fastest in the SA node and slowest in the His-Purkinje system: SA node > AV node > His - Purkinje Pacemaker potential: Self-excitation of SA node: What causes the SA node to fire spontaneously?  SA node fires 70 or 80 times per minute under the effect of vagal tone.  The cells of the SA node do not maintain a resting membrane potential in the manner of resting neurons or skeletal muscle cells.  Instead, during the period of diastole, the SA node exhibits a slow spontaneous depolarization called the pacemaker potential (prepotential).  This is due to the inherent leakiness of the SA nodal fibers to Ca +2 ions that causes this self-excitation (Ca+2 influx).  The membrane potential begins at about (–60 mV) and gradually depolarizes to (–40 mV), which is the threshold for producing an action potential in these cells.  This spontaneous depolarization is produced by the diffusion of Ca+2 through openings in the membrane called slow calcium channels.  At the threshold level of depolarization, other channels called fast calcium channels open and Ca+2 rapidly diffuses into the cells  Repolarization is produced by the opening of K+ gates and outward diffusion of K+, as in the other excitable tissues.  Once repolarization to –60 mV has been achieved, a new pacemaker potential begins, again culminating with a new action potential at the end of diastole.  There are three pairs of internodal tracts through which impulse passes from SA node to AV node fibres.  Impulse reaches AV node within 0.03 sec after its origin in SA node.  At AV node, there is a delay of 0.09 second and further delay in ‘bundle of His’, for 0.04 second (total delay is 0.13 second). Causes of AV nodal delay 1- Fibres connecting internodal tract and AV node are called transitional fibres.  These are very small fibres conducting the impulse at a very slow rate, i.e. 0.02 to 0.05 m/s. 2- Velocity of impulse conduction in AV nodal fibres is also slow, i.e. 0.05 m/s. 3-There are very few gap junctions connecting successive fibres in the pathway.  Bundle of His conducts impulse from AV node to its left and right branches.  Except in certain abnormal states, fibres of AV bundle conduct the impulse from atria to ventricle and not in the reverse direction.  This allows forward conduction of impulse.  Atrial muscle is separated from ventricular muscle by a continuous fibrous barrier which acts as a barrier to passage of impulse through any other route from atria to ventricles except through AV bundle.  AV bundle passes downward in ventricular septum for 5 to 15 mm and then divides into left and right bundle branches.  Through these branches, impulse passes to two ventricles.  Branches divide into Purkinje fibres which become continuous with cardiac muscle fibres.  The time taken for impulse to travel from bundle branches to Purkinje fibres is 0.03 second.  Through Purkinje fibres, impulse is spread rapidly to ventricular muscle fibres.  The velocity of transmission of impulse in ventricular muscle fibres is 0.3 to 0.5 m/s.  It first spreads over the endocardial surface and then the cardiac muscle fibres  Therefore, transmission from endocardial surface to epicardial surface takes about 0.03 second.  The total time for transmission in normal heart from initial bundle branches to ventricles is 0.06 second.  When the cholinergic vagal fibers to nodal tissue are stimulated the membrane becomes hyperpolarized and the slope of the prepotentials is decreased because the acetylcholine released at the nerve endings increases the K+ conductance of nodal tissue. acetylcholine  This action is mediated by M2 muscarinic receptors which opens a special set of K+ channels slowing the prepotential.  Activation of the M2 receptors decreases cyclic adenosine 3',5'- monophosphate (cAMP) in the cells, and this slows the opening of the Ca+2 channels.  The result is a decrease in firing rate.  Strong vagal stimulation may abolish spontaneous discharge for some time.  Conversely, stimulation of the sympathetic cardiac nerves speeds the depolarization in the prepotential and the rate of spontaneous discharge increases.  Norepinephrine secreted by the sympathetic endings binds to β1 receptors, and the resulting increase in intracellular cAMP facilitates the opening of Ca+2 channels, increasing the rapidity of the depolarization phase of the impulse. What is the duration of contraction in cardiac muscle?  Duration of contraction for atrial muscle is 0.1 second and for ventricular muscle is 0.3 second. What is ectopic pacemaker?  When pacemaker is other than SA node it is called ectopic pacemaker, e.g. AV node or Punkinje fibres may act as pacemakers.  Ectopic pacemaker causes abnormal sequence of contraction of different parts of the heart. Applied Aspect What are the causes of shift of pacemaker?  Causes of shift of pacemaker from SA node to other sites are: 1.Rate of discharge in other parts of the heart becomes higher than that of SA node. 2.Blockage of transmission of impulse from SA node to AV node. What is the importance of AV nodal delay? Atria and ventricles are excited at different times and also contract at different times because of AV nodal delay. What is the resting membrane potential of normal cardiac muscle? Resting membrane potential of normal cardiac muscle is −85 to –95 mV.  Ionic basis of the action potential of the ventricular cardiac muscle fiber cell:  The action potential of ventricular cardiac muscle fiber cell includes the following phases:  Phase 0 (upstroke): initial rapid depolarization with an overshoot to about +20 mV are due to opening of the voltage-gated Na+ channels with rapid Na+ influx.  Phase 1 (partial repolarization): initial rapid repolarization is due to K+ efflux (K+ outflow) followed the closure of Na+ channels when the voltage reaches at nearly +20 mV. Phase 2 (plateau): subsequent prolonged plateau is due to slower and prolonged opening of the voltage-gated Ca+2 channels with Ca+2 influx, Ca+2 enter through these channels prolong depolarization of membrane. Phase 3 (rapid repolarization): final repolarization is due to opening of the voltage-gated K+ channels at zero voltage with rapid K+ outflow (K+ efflux) followed the closure of Ca+2 channels and, this restores the membrane to its resting potential. Phase 4 (complete repolarization): The membrane potential goes back to the resting level (- 90 mV) i.e., restoration of the resting potential. This is achieved by the Na+-K+ pump that works to move the excess K+ in and the excess Na+ out. What is the cause of plateau recorded in cardiac muscle action potential? Plateau is due to: 1.opening of slow voltage-gated calcium sodium channels through which calcium and sodium ions continue to diffuse into the fibre.  This causes prolonged phase of depolarization, i.e. plateau. 2. At the onset of action potential, permeability of membrane for potassium decreases about fivefold.  This greatly decreases potassium outflux during action potential plateau and thereby prevents repolarization.  When slow calcium-sodium channels close at the end of 0.2 to 0.3 second, then membrane permeability for potassium rapidly increases causing rapid outflux of potassium.  This results into returning of membrane potential to resting level (repolarization). Which of the following is the result of an inward Na+ current? (A) Upstroke of the action potential in the sinoatrial (SA) node (B) Upstroke of the action potential in Purkinje fibers (C) Plateau of the action potential in ventricular muscle (D) Repolarization of the action potential in ventricular muscle (E) Repolarization of the action potential in the SA node Refractory period:  Absolute refractory period (ARP), it is the interval during which no action potential can be produced, regardless of the stimulus intensity i.e., no stimulus however strong can produce a propagated action potential.  It lasts the upstroke plus plateau and initial repolarization till mid- repolarization at about -50 to -60 mV, about 0.25 to 0.30 second.  It means that the cardiac muscle can not be re-exited during the whole period of systole and early part of diastole.  This period prevents waves summation and tetanus.  Relative refractory period (RRP), it is the interval during which the muscle is more difficult than normal to excite but nevertheless can be excited by a very strong excitatory signal.  It lasts about 0.05 second from the end of ARP (mid- repolarization) and ends shortly before complete repolarization i.e., it lasts for a short period during diastole. Refractory Periods Skeletal Muscle Cardiac Muscle Cardiac muscle structure Myocardial cell structure 1. Sarcomere is the contractile unit of the myocardial cell. is similar to the contractile unit in skeletal muscle. runs from Z line to Z line. contains thick filaments (myosin) and thin filaments (actin, troponin, tropomyosin). As in skeletal muscle, shortening occurs according to a sliding filament model, which states that thin filaments slide along adjacent thick filaments by forming and breaking cross-bridges between actin and myosin. Sliding Filament Mechanism  Cardiac muscle shortens during contraction because the thick and thin filaments slide past one another..  Muscle contraction occurs because myosin heads attach to and “walk” along the thin filaments at both ends of a sarcomere, progressively pulling the thin filaments toward the M line. Explain phenomenon of excitation-contraction coupling in the cardiac muscle?  Sarcoplasmic reticulum in the cardiac muscle is less well developed than in skeletal muscle.  It is present as a network of tubules surrounding the myofibrils.  It has dilated terminals (cisternae) which are located next to the external cell membrane and Ttubules.  Sarcoplasmic reticulum and cisternae contain high concentration of ionic calcium.  T tubules are continuations of cell membrane and they conduct action potential to the interior of the cell.  They invaginate to the interior of the cell at the ‘Z’ line of sarcomere.  There is only one T tubule present per sarcomere.  Are well developed in the ventricles, but poorly developed in the atria.  Form dyads with the sarcoplasmic reticulum.  When action potential passes over the cardiac muscle membrane, it passes to the interior of the muscle cells through T tubules.  Action potential acts on the membranes of longitudinal sarcoplasmic tubules to cause instantaneous release of calcium.  Calcium ions diffuse into the myofibrils and catalyze chemical reactions that promote sliding of actin and myosin filaments which in turn produce muscle contraction.  In cardiac muscle (as against that in skeletal muscle) extra calcium ions diffuse into the sarcoplasm from ‘T’ tubules.  T’ tubules of cardiac muscle contain mucopolysaccharides which are negatively charged and bind an abundant store of calcium ions.  ‘T’ tubules open directly to the exterior and therefore calcium ions directly come from extracellular fluid.  These calcium ions diffuse into the sarcoplasm when action potential propagates along the ‘T’ tubules.  Because of this, strength of cardiac muscle contraction depends to a great extent on calcium concentration in extracellular fluid.  Whereas skeletal muscle contraction is hardly affected by calcium concentration in ICF.   Sarcoplasmic reticulum (SR) are small-diameter tubules in close proximity to the contractile elements. are the site of storage and release of Ca2+ for excitation–contraction coupling.  During the plateau of the action potential, Ca2+ conductance is increased and Ca2+ F enters the cell from the extracellular fluid (inward Ca2+ current) through L-type Ca2+ O channels (dihydropyridine receptors). O T  This Ca2+ entry triggers the release of even more Ca2+ from the SR (Ca2+-induced E Ca2+ release) through Ca2+ release channels (ryanodine receptors). R  The amount of Ca2+ released from the SR depends on the amount of Ca2+ previously stored and on the size of the inward Ca2+ current during the plateau of the action potential.  As a result of this Ca2+ release, intracellular [Ca2+] increases.  Ca2+ binds to troponin C, and tropomyosin is moved out of the way, removing the inhibition of actin and myosin binding.  Actin and myosin bind, the thick and thin filaments slide past each other, and the myocardial cell contracts.  The magnitude of the tension that develops is proportional to the intracellular [Ca2+].  Relaxation occurs when Ca2+ is reaccumulated by the SR by an active Ca2+-ATPase pump.