Review of Myocardial Function Action Potentials PDF

Y1B6M1L2 CARDIOVASCULAR SYSTEM, RESPIRATORY LECTURER: GILBERT GUY MURILLO, M.D. SYSTEM, BLOOD & LYMPHATICS INTEGRATION JANUARY 16, 2024 | 8:00-10:00 RE...

Y1B6M1L2 CARDIOVASCULAR SYSTEM, RESPIRATORY LECTURER: GILBERT GUY MURILLO, M.D. SYSTEM, BLOOD & LYMPHATICS INTEGRATION JANUARY 16, 2024 | 8:00-10:00 REVIEW OF MYOCARDIAL FUNCTION AND ACTION POTENTIALS TABLE OF CONTENTS But smaller than Fiber length Large (50-100 μm) skeletal muscles I. Cardiac Muscle III. Action Potentials in Cardiac A. Cardiac vs. Skeletal vs. Muscle Epimysium is Connective tissue Endomysium Smooth Muscles A. Resting Membrane found in skeletal components Perimysium B. Three Major Types of Potential (RMP) muscles only Cardiac Muscle B. Action Potential (AP) II. Physiologic Anatomy of C. Phases of Cardiac Contractile proteins organized into Organization Cardiac Muscle Muscle Action Potential sarcomeres A. Cardiac Muscle As A D. Mechanism of Muscle Syncytium Contraction Regular proteins for Troponin E. Excitation-Contraction contraction Tropomyosin Coupling IV. Summary Sarcoplasmic Some (less compared to skeletal V. Review Questions reticulum muscles) I. CARDIAC MUSCLE 5x larger than skeletal, aligned with Z disks ○ vs. A-I band junctions in skeletal muscles Transverse tubules T-tubules - extensions of cell present membranes penetrating to the muscle cells ○ Allow rapid and equally distributed transmission of action potential (AP) Gap junctions and desmosomes Junction between in intercalated discs fibers Intercalated discs - facilitate faster spread of AP Autorhythmicity Yes Sarcoplasmic reticulum Source of calcium Interstitial fluid for contraction ○ Via T-tubules for adequate source and stronger contraction Moderate Figure 1. Structure of the heart and course of blood flow through Speed of ○ To allow adequate filling as the heart chambers and valves (Guyton & Hall, 13E) contraction heart functions as a pump to fill the circulatory system with blood Table 1. Characteristics of cardiac muscle tissue (Tortora’s) CHARACTERISTIC DESCRIPTION Nervous control Involuntary – controlled by ANS Striated Acetylcholine and norepinephrine Microscopic ○ Released by autonomic motor Branched, cylindrical fiber appearance and neurons feature Single centrally located nucleus Regulators Joined by intercalated disks Several hormones Regulate heart rate, conduction Location Heart velocity, and contractility Larger than Capacity for Limited Fiber diameter Large (10-20 μm) regeneration Under certain conditions smooth muscles 🔊🗃️ MG 9 | MG 12 1 of 10  Y1B6M1L2: REVIEW OF MYOCARDIAL FUNCTION ACTION POTENTIALS A. CARDIAC VS. SKELETAL VS. SMOOTH MUSCLES *see Table 2 located in the appendix section. B. THREE MAJOR TYPES OF CARDIAC MUSCLES Table 3. Three Major Types of Cardiac Muscles TYPE DESCRIPTION Atrial Muscle Contract like skeletal muscles but with a longer duration ○ To allow adequate filling of the Ventricular Muscle heart Exhibits weaker contractions due to fewer contractile fibers Specialized Exhibits either automatic Excitatory and rhythmical electrical discharge as Conductive AP or conduction of the AP through Figure 2. SA nodal tissue (red) is found in the right atrium at the Muscle Fibers the heart, providing an excitatory junction of the crista terminalis and the intercaval region system that controls the rhythmical cardiac beating SPECIALIZED EXCITATORY AND CONDUCTIVE SYSTEM OF THE HEART AUTORHYTHMICITY Ability to generate spontaneous action potentials Autorhythmic Fibers - repeatedly generate action potentials that trigger heart contractions ○ Continue to stimulate the heart to beat even after it is removed from the body (e.g. during transplantation) Tissues that have autorhythmicity: ○ SA Node - dominant/natural pacemaker ○ AV Node - main communication of action potentials to the ventricles → Causes delay between atrial and ventricular systole to facilitate thorough filling of ventricles before pumping it to the system → Damage (e.g. during infarction) causes the activation of Figure 3. Atrial tracts in the heart (Atrial tracts allow initial atrial ectopic pacemakers causing arrhythmia and other contraction before the ventricles. Atria acts as a primary pump, rhythmic problems increasing the ventricular pump effectiveness to as much as 20%) CONDUCTION SYSTEM Network of specialized cardiac muscle fibers that provide a path for each cardiac excitation to progress through the heart Facilitates the spread of AP throughout the contractile atrial and ventricular muscles Composition of the conduction system: ○ Internodal Tracts → Inter-auricular tract (Bachmann’s bundle) → Anterior, Middle, and Posterior Tracts ○ His-Purkinje System - distribute action potentials to myocardium → AV bundle (Bundle of His) - specialized conductive system of fibers that allows one-way (forward) conduction of potentials from the atria to the ventricles but prevents conduction the other way around Figure 4. Sinus node and the Purkinje system of the heart, also showing the A-V node, atrial internodal pathways, and ventricular bundle branches MG 9 | MG 12 2 of 10  Y1B6M1L2: REVIEW OF MYOCARDIAL FUNCTION ACTION POTENTIALS Table 4. Description of terms INTERCALATED DISCS (ID) TERMS DESCRIPTION Intercalated Discs (ID) - dark areas crossing the cardiac Specialized Excitatory and muscle fibers Conductive System of the Controls cardiac contractions ○ Fusion of cell membranes that separate individual cardiac Heart muscle cells from one another ○ Complex adhering structures that connect single Sinus Node In which normal rhythmical cardiac myocytes to a syncytium (Sinoatrial/S-A Node) impulses are generated ○ Responsible for force transmission during contraction ○ Provides a strong union between fibers, maintaining Conduct impulses from the Internodal Pathways cell-to-cell cohesion S-A node → A-V node → So that the pull of one contractile unit can be In which impulses from the atria transmitted along its axis to the next unit A-V node are delayed before passing into the ventricles A. CARDIAC MUSCLE AS A SYNCYTIUM Conducts impulses from the ARCHITECTURE A-V bundle atria → ventricles Latticework, with fibers dividing, recombining, and then Left and Right Bundle Conduct the cardiac impulses to spreading again Branches of Purkinje Fibers all parts of the ventricles ○ Different from skeletal muscles which have individual fibers bound into a bundle II. PHYSIOLOGIC ANATOMY OF CARDIAC MUSCLE → Like “walis tambo” Intercalated Discs - separates individual muscles from one At the end of the systole, the left ventricle is like a loaded another spring and recoils or untwists during diastole (relaxation) ○ Cell membranes fuse with one another to form permeable ○ To allow blood to enter the pumping chambers rapidly communication junctions (gap junctions) ○ Endocardial and Epicardial Fibers - oppositely oriented → Allow rapid diffusion of ions, and thereby faster helices spread of AP from one cardiac muscle cell to another → Unique fiber organization of the heart to become an ○ Presence of intercalated discs and structures within, allow effective pump individual and distinct cardiac cells to communicate and move as one, as if it is a whole structure → Executing a synchronous contraction, thus a syncytium Figure 5. A: Left ventricular inner subendocardial fibers (lavender) run obliquely to the outer subepicardial fibers (red). B: Subepicardial muscle fibers are wrapped in a left-handed helix Figure 6. Longitudinal sections of cardiac muscles showing widely and subendocardial fibers are arranged in a right-handed helix spaced intercalated discs (I), centrally located nuclei (N), and Additional Notes from Dagitab Trans:: closely spaced striations (S) Cardiac muscle - syncytium of many interconnected cardiac cells TYPES OF CARDIAC SYNCYTIA ○ Functions of the cardiac cells in the syncytium: Table 5. Types of cardiac syncytia → Allows rapid spread of action potential → Allows synchronized contraction of myocardium TYPE DESCRIPTION Cardiac Muscle Cell - essential long, cylindrical cell with one or two nuclei that are centrally located within the cell Atrial Syncytia Constitutes the wall of atria Cardiac Muscle Tissue - arranged in a latticework (cells are interdigitating) Ventricular Constitutes the wall of ventricles Myofibrils contain actin and myosin filaments that are Syncytia almost identical to those found in skeletal muscles The syncytia are separated by a fibrous tissue surrounding the T-tubules in the Cardiac Muscle - larger and broader AV valvular openings between the atrial and ventricular ○ Run along Z-disks syncytia MG 9 | MG 12 3 of 10  Y1B6M1L2: REVIEW OF MYOCARDIAL FUNCTION ACTION POTENTIALS Atrial syncytium is able to move independently from its ventricular counterpart → Allowing the atria a short time ahead a ventricular contraction Necessary for heart filling and pumping THREE TYPES OF CELL-TO-CELL JUNCTIONS Figure 8. TEM of an intercalated disc (arrows) shows a steplike structure. In Figure 8: ○ Transverse regions of the disc have many desmosomes (D) and adherent junctions called fascia adherens (F) → Fascia adherens - point of contact between myocytes ○ Less electron-dense regions of the disc have abundant Figure 7. Cell junctions of epithelia (e: gap junction; c: desmosome gap junctions = macula adherens; b: adherens junction/zonula adherens = fascia → Contribute greatly to the syncytium property of heart adherens) * (=): counterpart in myocytes muscles ○ The sarcoplasm has numerous mitochondria (M) to feed FASCIA ADHERENS the high energy demand Predominant type Increases surface area of contact within each myocyte III. ACTION POTENTIAL IN CARDIAC MUSCLE Equivalent of zonula adherens in epithelial cells A. RESTING MEMBRANE POTENTIAL Follow a ribbon-like pattern and does not completely enclose the cell Resting Membrane Potential (RMP) - intracellular charge Primarily keep myocytes together during contraction ○ Exhibited by ALL cells, unlike action potential that exists only in excitable cells MACULA ADHERENS ○ Driven by concentration differences of various ions (mainly K+ and Na+) Reinforces point of contact between myocytes → Each attempt to drive membrane potential towards its Cause tight intercellular adhesion that keep myocytes together equilibrium potential (Nernst Potential) during contraction and relaxation ○ Normal RMP = -85 mV to -90 mV → Mnemonic: PISO -> 2-PISO-3 GAP JUNCTIONS (NEXUS JUNCTIONS) 2 Potassium In, 3 Sodium Out Sites of low electrical resistance that act as low-resistance ⎻ Potassium - predominant cation INSIDE the cell bridges for easy spread of fiber excitation ⎻ Sodium - predominant cation OUTSIDE the cell Permit the cardiac muscle to function as a syncytium without ⎻ Sodium-Potassium ATPase Pump - keeps the protoplasmic bridges concentration gradient in all cells Act as a gateway for AP for easy spread of among myocytes, As more positive ions GO OUT, RMP becomes creating a synchronous contraction more negative B. ACTION POTENTIAL (AP) Additional Information From Dagitab: Fascia Adherens Only found in excitable cells (e.g. neurons, muscles) ○ Composed of depolarization/upstroke and repolarization ○ Actin filament-anchoring adherens junctions (return to RMP) Macula Adherens ○ Intermediate filament-anchoring desmosomes Table 6. Characteristics of a True Action Potential (AP) AV bundle (Atrial-Ventricular Bundle) - specialized CHARACTERISTICS DESCRIPTION conductive system of fibers that allows one-way (forward) conduction of potentials from atria to ventricles, but prevents y-axis = membrane potential in conduction the other way around Stereotypical Size millivolt ○ Allows atria to contract ahead of the ventricles for and Shape x-axis = time in seconds effective heart pumping MG 9 | MG 12 4 of 10  Y1B6M1L2: REVIEW OF MYOCARDIAL FUNCTION ACTION POTENTIALS NORMAL VALUES TO REMEMBER Causes depolarization of adjacent cells in a non-decremental manner Table 7. Normal Values Propagating Spreads without decreasing in conduction magnitude PHASE VALUE Unless a threshold is reached, as Normal RMP -85 mV to -90 mV All-or-None those in acute subthreshold potentials, an action potential will NOT proceed Action Potential (Ventricular Muscle 105 mV Fiber) Duration of Atrial Depolarization 0.2 s Duration of Ventricular Depolarization 0.3 s Depolarization (in total) 2 ms Plateau Phase + Repolarization ≥ 200 ms Cardiac muscles - contract longer than skeletal muscles ○ Due to plateau phase and repolarization ○ Prolonged strong contraction allows heart to pump continuously to distribute blood throughout the body Additional Notes from Dagitab Trans: REASONS WHY DEPOLARIZATION IN CARDIAC MUSCLE CELL IS PROLONGED Fast sodium channels (same with skeletal muscles) Figure 9. Action potential of purkinje fibers and ventricular muscles abruptly close Figure 9 shows the characteristics of true AP: L-type calcium channels/slow calcium channels/ ○ There is consistency and uniformity in each action calcium-sodium channels that are slow to open and potential. slower to close, let both calcium and sodium through ○ The propagation in adjacent myocytes occurs through gap At the action potential onset, there is a decrease in the junctions found in the intercalated discs, creating a uniform permeability of potassium, thus repolarization takes longer to and unified contraction. start. ○ Once a threshold potential is reached, action potential will proceed. REPOLARIZATION IS NOT COMPLETE UNTIL CONTRACTION IS HALF OVER Table 8. Changes in the External Potassium and Sodium Concentration CHANGES WHAT IT AFFECTS Changes in the external Affect the RMP of the cardiac K+ concentration muscle Changes in the external Affect the magnitude of the Na+ concentration action potential KEY IONIC CHANNELS IN CARDIAC MUSCLES Figure 10. Action potential threshold Voltage-gated fast sodium channels (opens at -70 to -80 mV) Figure 10 graph illustrates the basic need to reach a threshold ○ This is the area where the threshold is reached before it membrane potential to create an action potential. upshoots to become a true action potential ○ For as long as a threshold potential is not reached, an Fast potassium channels - opens on repolarization action potential will not proceed L-type calcium channels/slow calcium channels/ calcium-sodium channels ○ Activated at -30 to -40 mV ○ Responsible for the plateau phase of the action potential = prolonging cardiac contraction ○ Not only opens slowly, but also allows sodium to flow in with calcium MG 9 | MG 12 5 of 10  Y1B6M1L2: REVIEW OF MYOCARDIAL FUNCTION ACTION POTENTIALS Table 9. Key ionic channels in cardiac muscles Slow calcium channels reach maximal opening and significant effect on membrane potential when sodium Ionic Channel Description channels are completely closed. Lesser cations flow inside (Na+), more cations flow outside (K+) Opens at -70 to -80 mV Membrane potential becomes more negative Voltage-gated fast ○ Area where the threshold is sodium channels reached before it upshoots to PHASE 2 (PLATEAU) become a true action potential Around -30mV to -40mV Fast potassium Slow Ca2+ channels open = Ca2+ influx Opens on repolarization ○ Only contributes insignificantly channels ○ Reaches maximal opening and significant effect on Activated at -30 to -40 mV membrane potential when Na+ channels are completely ○ During the upstroke of the closed and K+ outflows are decreasing (during Phase 1) L-type calcium Fast K+ channels close slowly with decreased permeability = depolarization phase channels/Slow decreased K+ outflow Responsible for the plateau phase calcium channels/ A brief initial repolarization occurs and the action potential then of the action potential → prolonging Calcium-sodium plateaus because of: cardiac contraction channels ○ Increased Ca2+ ion permeability Opens slowly Allows Na+ to flow in with Ca2+ ○ Decreased K+ ion permeability ○ Voltage-gated calcium ion channels open slowly during Resting Membrane Potential phase 1 and 0 ○ PISO: Potassium Influx, Sodium Outflow → Calcium enters the cell → Drive RMP to -85 to -90 mV ○ Potassium channels then close and the combination of Cardiac Action Potential decreased potassium ion efflux and increased calcium ion ○ POSI + CALI: Potassium Outflow, Sodium Influx, CALcium influx causes the action potential to plateau Influx → Opposing the full repolarization ○ Allow Na+ influx (calcium-sodium channel), thus greatly C. PHASES OF CARDIAC MUSCLE ACTION POTENTIAL opposing the decreasing membrane potential upon reaching maximal opening. PHASE 4 (RESTING MEMBRANE POTENTIAL) RMP phase at -90 mV PHASE 3 (RAPID REPOLARIZATION) Final phase PHASE 0 (UPSTROKE/DEPOLARIZATION) Slow Ca2+ start to close Fast Na+ channels first to open = Na+ influx Fast K+ channels open = K+ outflow Since there are more positive ions going in, the membrane Goes back to RMP (phase 4 at -90mV) potential becomes more positive ○ Approximately +105 mV (depolarization membrane potential) When the cardiac cell is stimulated and depolarizes, the membrane potential becomes more positive Membrane potential reaches about +20 millivolts before the sodium channels close Slow Calcium Channel (around -30 to –40 mV) slowly starts to open causing slow Ca2+ influx, but does not contribute significantly Lecturer Notes: POSI-CALI ○ During cardiac action potential, Na+ will flow inside the cells. Upon reaching maximum Na+ influx and channel closure, the Figure 11. Phases of cardiac muscle action potential fast Na+ channels start to open. Fast Na+ channels open → Fast K+ channels open Still using POSI-CALI, once K+ channels open, outflow of K+ cations happens. Now, less cations (Na+) flow inside and more cations flow outside. The membrane potential becomes more negative. This is the Phase 1 or Initial Repolarization. PHASE 1 (INITIAL REPOLARIZATION) Fast Na+ channels close Fast K+ channels open = K+ outflow Figure 12. The associated ionic currents for sodium (iNa+), calcium (iCa2+, and potassium (iK+). MG 9 | MG 12 6 of 10  Y1B6M1L2: REVIEW OF MYOCARDIAL FUNCTION ACTION POTENTIALS SUMMARY OF CARDIAC MUSCLE ACTION POTENTIAL Action Potential → Muscle Contraction Muscle contraction of the heart starts at depolarization and 3 main ionic channels that close and open as the action lasts longer than 1.5x than the AP due to the plateau phase. potential phases happen: Na+, K+, Ca2+ Table 10. Summary Of Phases Of Cardiac Muscle Action Potential STEPS PHASE DESCRIPTION 1. As is true for skeletal muscles, when an AP passes over the cardiac muscle membrane, AP spreads to the interior of the Phase 4 RMP phase at -90 mV cardiac muscle fiber along the membranes of the transverse (Resting Membrane K+ outflow complete the tubules (T-tubules). Potential) repolarization 2. AP then acts on the membranes of the sarcoplasmic tubules ○ Causes the release of Ca2+ ions into the muscle At RMP: Fast Na+ channels first to cytoplasm from the sarcoplasmic reticulum. Phase 0 3. These Ca2+ ions will eventually diffuse into the myofibrils and open = Na+ influx (Upstroke/ catalyze the chemical reaction that promotes sliding of actin -30 to -40 mV: Slow Ca2+ channel Depolarization) and myosin filaments along one another. open ○ Produces muscle contraction Fast Na+ channels close → Similar to skeletal muscle Phase 1 (Initial Fast K+ channels open = K+ outflow Calcium-Induced-Calcium-Release System - unique to Repolarization) ○ Membrane potential become cardiac muscles more negative ○ NOT found in skeletal muscles ○ Allows cardiac muscles to maintain powerful and strong Slow Ca2+ channels reach peak contraction to do its function as a pump since it has an opening = Ca2+ and Na+ influx underdeveloped sarcoplasmic reticulum Phase 2 (Plateau) ○ Causes plateau → Cannot store enough Ca2+ to reach full contraction Fast K+ channels close slowly with ○ To compensate, larger cardiac T-tubules (invaginations of decreased K+ permeability/outflow cytoplasm into the muscle cells) that also contain large amounts of mucopolysaccharides allow greater quantities Slow Ca2+ channels close of Ca2+ to be stored. Phase 3 (Rapid Fast K+ channels open = K+ outflow ○ Two sources of Ca2+: Repolarization) ○ Increased K+ permeability → T-Tubules (Extracellular) Going back to RMP → Sarcoplasmic Reticulum How Ca2+ Causes Cardiac Contraction: 1. Once an AP reaches the T-tubules, voltage-dependent EXCITABILITY Ca2+ channels (dihydropyridine channels) open and Absolute Refractory Period - AP cannot be elicited at Phase release stored Ca2+ towards the inside of the cell 0 to 2 2. Ca2+ will interact with ryanodine receptor channels Effective Refractory Period - AP cannot be elicited at FIRST (found on the surface of sarcoplasmic reticulum), triggering half of Phase 3 further release of Ca2+ into the sarcomere Relative Refractory Period - AP can be elicited by a very 3. Cardiac contraction occurs strong signal during the LAST half of Phase 3 to 4 Cardiac muscle is affected by Ca2+ in the ECF Refractory periods allow a rhythmic contraction of the muscles ○ In contrast to skeletal muscle contraction that is hardly and protects them from strain by not allowing them to contract affected by moderate changes in ECF Ca2+ concentration while already contracting. ○ Hypo/Hypercalcemia state greatly affects cardiac function D. MECHANISM OF MUSCLE CONTRACTION At the end of the plateau of the cardiac AP, the influx of Ca2+ ions to the interior of the muscle fiber is suddenly cut off ○ There is no longer depolarization reaching the L-type Ca2+ channel ○ Ca2+ ions in the sarcoplasm are rapidly pumped back OUT of the muscle fibers and stored in the sarcoplasmic reticulum and out INTO the cell. → Transport of Ca2+ back into the sarcoplasmic reticulum is achieved with the help of a calcium-adenosine triphosphatase (ATPase) pump (the sarcoplasmic endoplasmic reticulum calcium ATPase, SERCA2) ○ Na+ that enters the cell during this exchange is then transported out of the cell by the Na-K ATPase pump Contraction ceases until a new action potential comes along, causing the contraction. Figure 11. Mechanism of Muscle Contraction MG 9 | MG 12 7 of 10  Y1B6M1L2: REVIEW OF MYOCARDIAL FUNCTION ACTION POTENTIALS Additional Information from Dagitab Trans: 3. Ca2+ released from the sarcoplasmic reticulum binds to the actin (thin) filaments which initiates sarcomere contraction. ROLE OF SODIUM AND CALCIUM CHANNELS 4. At the end of the contraction sequence, Ca2+ comes off of the Voltage-gated Na+ channel in cardiac muscle has two myofilaments and is actively transported back into the gates: sarcoplasmic reticulum by the calcium pump. ○ Outer gate - opens at the start of depolarization 5. Ca2+ is also transported into the extracellular space by a (membrane potential of -70 to -80 mV) membrane-bound sodium-calcium exchanger pump ○ Inner gate - then closes and precludes further influx until Cardiac contraction is brought about by actin (thin) filament the action potential ends (sodium channel activation) and myosin cross-bridges (projecting from the thick -30 to -40 mV - slow calcium channel is activated at this filament) interaction. membrane potential RELAXED CARDIAC MUSCLE TYPES OF POTASSIUM ION CHANNELS THAT PRODUCE Troponin and tropomyosin conformation prevent actin from REPOLARIZATION interacting with the myosin cross-bridges that contain bound Table 10. Types of Potassium Ion Channels that Produce ATP. Repolarization ACTIVATED CARDIAC MUSCLE TYPES DESCRIPTION 2+ Ca binds to Troponin C, which shifts troponin complex and tropomyosin to an active conformation Produces transient, early outward current ○ Enables actin to interact with myosin cross-bridges. First Type that produces an early incomplete Myosin ATPase on the myosin heads hydrolyzes ATP, thus repolarization providing the requisite energy for the myosin cross-bridges to interact with actin. Inwardly rectifying, i.e., at plateau potentials Myosin cross-bridges then pull the actin thin filaments towards it allows K+ influx but resists K+ efflux, and the center of the sarcomere. Second Type only at lower membrane potentials does it permit K+ efflux; the current it produces is IV. SUMMARY called IKr Cardiac muscle cells are long, cylindrical with one or two A slowly activating delayed rectifying type centrally located nuclei. Third Type Myofibrils are almost identical to those in skeletal muscles. that produces a current called IKs Intercalated discs are dark areas crossing the fibers. These are Sum of IKr and Small net outward current that increases fused cell membranes (via gap junction) that separate a IKs with time and produces repolarization cardiac cell from another. 3 types of intercalated disc cell-to-cell junction ○ Fascia adherens – actin filament-anchoring adherens junctions. Increases surface area of contact. E. EXCITATION - CONTRACTION COUPLING IN THE HEART → Predominant type of contact Myocardium – composed of cardiac myocyte and ○ Macula adherens - intermediate filament-anchoring non-myocyte cells. desmosomes. Tight intercellular adhesion. The process of excitation-contraction coupling becomes ○ Gap junctions (Nexus junctions) – sites of low electrical dysregulated in cardiac hypertrophy and cardiac failure. resistance that provide low-resistance bridges for easy spread of fiber excitation CARDIAC MYOCYTES Resting Membrane Potential (RMP) is the intracellular charge and is exhibited by all cells. Make up ~70% of the mass of the heart. ○ 2-PISO-3 (2 Potassium In, 3 Sodium Out) Meshed in a collagen network that acts as a supporting Action Potential (AP) is only found in excitable cells (e.g., all framework. muscle types and neurons) Blood is supplied to individual cardiac myocytes through Two components of AP: capillaries that are near them. ○ Depolarization or upstroke Comprised of actin and myosin myofilaments ○ Repolarization or the return to RMP ○ Organization gives rise to the striated appearance of Characteristics of true AP: cardiac muscle ○ Stereotypical size and shape 2 Prominent Organelles Within Cardiac Myocytes: ○ Propagating ○ Mitochondria - produce energy ○ All-or-none ○ Sarcoplasmic reticulum - regulates Ca2+ handling in the Phases of Cardiac Action Potential cell ○ PHASE 4 – Resting Membrane Potential ○ PHASE 0 – Upstroke/Depolarization INITIATION OF CARDIAC CONTRACTION ○ PHASE 1 – Initial Repolarization 1. Extracellular calcium moves into the cell across the ○ PHASE 2 – Plateau voltage-dependent L-type calcium channel. ○ PHASE 3 – Rapid Repolarization 2. Ca2+ that enters the cell triggers Ca2+ release from the ryanodine receptor through a process called calcium-triggered calcium release/calcium-induced calcium release. MG 9 | MG 12 8 of 10  Y1B6M1L2: REVIEW OF MYOCARDIAL FUNCTION ACTION POTENTIALS V. REVIEW QUESTIONS C. Sarcoplasmic reticulum & Golgi apparatus D. Mitochondria & Lysosome 1. What is the main communication of action potentials to ventricles? A. Bundle of His ANSWERS: 1C 2D 3A 4A 5A 6C 7B 8B 9D 10A B. SA node C. AV node References: D. VA node Costanzo, Linda S. BRS Physiology. 6th ed., Wolters 2. Which of the following is NOT a type of cell-to-cell junction Kluwer, 2015. found in myocytes? Hall, J. E. (2016). Guyton and Hall Textbook of Medical A. Gap junctions Physiology (13th ed.). Philadelphia: Elsevier, Inc. B. Fascia adherens “Heart: excitation-contraction coupling.” Youtube, C. Macula adherens uploaded by Björklund Nutrition, 14 Aug 2016. D. Desmosomes https://youtu.be/BxhlsbJacal 3. This permits the cardiac muscle to function as a syncytium Mescher, A. L. (2013). Junqueira's Basic Histology Text and without protoplasmic bridges: Atlas (13th ed.). McGraw-Hill Education. A. Nexus junctions Murillo, G.G.D. (2020). Review of Myocardial Function and B. Fascia adherens Action Potentials. C. Macula adherens Tortora, G. J. and Derrickson B. Principles of anatomy and D. Adherens junction physiology. 14th ed., John Wiley & Sons, Inc., 2014. WVSU-COM Batch DAGITAB. (2023). Physiology of 4. Which of the following is FALSE regarding resting membrane Cardiac Muscle, Action Potentials, and Conduction potential? Systems. A. Exhibited only by excitable cells Yartsev, Alex. “Excitatory, conductive and contractile B. As more positive ions go out, RMP becomes more negative elements of the heart.” 2020, derangedphysiology.com. C. Driven by concentration differences of various ions (mainly Accessed 16 Jan. 2024 K+ and Na+) D. None of the Choices 5. What is the cause of the Upstroke of AP in the SA node? Trans Team: A. Ca2+ influx MG 9: Agulan, Arenga, Bolaño, Duarte, Francisco, Nacionales, B. Na+ influx Pionelo, Señalista, Trespeces, Viaje C. K+ influx MG 12: Baga, Baranda, Catayas, Curias, Estimo, Hisuan, D. Cl- influx Maasin, Sasa, Tabat, Yadao 6. It is unique to excitable cells, namely neurons and certain types of muscle, and consists of two components: depolarization and repolarization. A. Resting Membrane Potential B. Graded Potential C. Action Potential D. Threshold Membrane Potential 7. What is the normal duration of ventricular depolarization? A. 0.1s B. 0.3s C. 0.7s D. 0.9s 8. During which stage of the cardiac muscle action potential does the permeability of potassium ions decrease while that of calcium ions increases? A. Initial Repolarization B. Plateau C. Rapid Repolarization D. Resting Membrane Potential 9. How does the excitation-contraction coupling of the cardiac muscle differ from other muscles? A. There is use of SR Ca2+ B. Action potential opens cell membrane voltage-gated Ca2+ channels C. Hormones and NTs open Inositol triphosphate-gated SR Ca2+ D. It utilizes Calcium-induced, Calcium-release system 10. What are the two prominent organelles within cardiac myocytes? A. Sarcoplasmic reticulum & Mitochondria B. Mitochondria & Golgi apparatus MG 9 | MG 12 9 of 10  Y1B6M1L2: REVIEW OF MYOCARDIAL FUNCTION ACTION POTENTIALS APPENDIX Table 2. Cardiac vs. Skeletal vs. Smooth Muscle CHARACTERISTIC CARDIAC SKELETAL SMOOTH Sarcomeres, Striations, ✖ ✓ ✓ Troponin (Calmodulin myosin light chain kinase) Ca2+ influx – SA Node Na+ influx – atria, ventricles Cause of Upstroke of AP - Purkinje fibers (exhibits Na+ influx Ca2+ influx prolonged action potential owed to prolonged sodium current) ✓ (Atria, Ventricles, Purkinje fibers) Plateau ✖ ✖ ↣⮽🗹 (SA Node) 150 ms (SA Node, Atria) AP Duration 250-300 ms (Ventricles, Purkinje 1 ms 10 ms fibers) AP opens cell membrane voltage-gated Ca2+ channels Excitation-Contraction Ca2+-induced Use of SR Ca2+ Coupling Ca22+-release Hormones and NTs open IP3-gated SR Ca2+ ✓ ✓ (only for unitary smooth Gap Junctions ✖ muscles) Number of SR In-between Greatest Least Regulation Actin-based using troponin Actin-based using troponin Myosin-based using MLCK *SA – sinoatrial; SR – sarcoplasmic reticulum; AP – action pote \ntial; IP3 – Inositol trisphosphate; MLCK – myosin light-chain kinase MG 9 | MG 12 10 of 10