Cardiac Electrophysiology & Anatomy (Lec 3)

Lecture 3: Coronary Perfusion and Cardiac Action Potentials

• The lecture covers coronary perfusion and cardiac action potentials.
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Orientation of the Heart

• Diagrams of the anterior and lateral views of the human heart, including the ribs, sternum, base of the heart, apex of the heart, and diaphragm, are provided.

Cardiac Cell Types

• The lecture discusses the types of cells found within the heart, but does not detail the specifics.

Why do we have a tricuspid and bicuspid valve?

• The lecture explores the function of tricuspid (right AV) and bicuspid (left AV) valves.
• Diagrams of the heart with labeled valves (tricuspid, mitral, aortic, pulmonary) are included.

Cardiac Muscle Cells - Intercalated Discs

• Intercalated discs are connecting junctions between cardiac cells, and include desmosomes (hold cells together) and gap junctions (electrically couple adjacent cells).
• These components allow the heart to function as a single coordinated unit.

Cardiac Muscle Cell Structure

• The microstructure of a cardiac muscle cell is illustrated.
• The cell components (mitochondria, T-tubule, sarcoplasmic reticulum, Z disc) are labeled in the diagram.

Cardiac Muscle vs Skeletal Muscle

• Cardiac muscle differs from skeletal muscle in its contraction mechanism and action potential characteristics.
• The difference in the duration of the action potential is essential to preventing sustained contractions.
• Cardiac muscle uses aerobic respiration exclusively.

Cardiomyocyte EC Coupling

• Strength of cardiac muscle contraction depends on the intracellular Ca²⁺ concentration.
• The SR does not store enough Ca²⁺ for efficient contraction.
• Ca²⁺ enters the sarcoplasm and stimulates the opening of ryanodine receptors on the SR.

Cardiac Muscle vs Skeletal Muscle

• Tetanic contractions cannot occur in cardiac muscle. It has a more prolonged refractory period compared to skeletal muscle. The longer refractory period allows the heart to relax and fill for efficient pumping.

Cardiac Muscle vs Skeletal Muscle respiration

• The heart relies on aerobic respiration. Cardiac muscle fibers have more mitochondria than skeletal muscle fibers.
• This is due to its greater dependence on oxygen. Both types of tissues can utilize other fuel sources. Cardiac muscle has greater adaptability to alternate fuels, but still needs oxygen.

The Heart is Metabolically Flexible

• The heart’s metabolic flexibility allows it to use different fuels like glucose, fatty acids, and ketone bodies even in a state of failure.
• Comparing a normal and failing heart illustrates the adaptable use of these fuels by the heart.

How do cardiomyocytes contract?

• The lecture explores the mechanisms of cardiomyocyte contraction, including initiation, propagation, and modification of contraction.

Setting the Basic Rhythm – Intrinsic conduction system

• A coordinated heartbeat is a function of the presence of gap junctions and the intrinsic cardiac conduction system.
• The intrinsic cardiac conduction system (network of non-contractile, autorhythmic cells) initiates and distributes impulses. This coordination facilitates heart depolarization and contraction.

Spread of Action Potentials

• Action potentials are locally initiated and conducted over the cell surface.
• They spread via direct contact with neighboring cells. Current passively depolarizes adjacent cells, initiating a new action potential.

Cell-Cell Conduction of Cardiac APs

• Action potentials spread between cardiomyocytes through gap junctions.

Speed of AP Propagation in Cardiac Tissue

• Conduction velocity is highly variable in different regions of the heart.
• Determined by factors like cardiomyocyte diameter, current intensity, and membrane resistance.

Intrinsic Conduction System

• The intrinsic conduction system (parts listed are) initiates and conducts the heartbeat. These parts are the sinoatrial (SA) node, internodal pathways, atrioventricular (AV) node, AV bundle, bundle branches, and Purkinje fibers.
• These parts work together to coordinate the contraction of the heart.

CT

• The image provides a histological view of parts of the heart where specific tissue structures are identifiable.
• Areas with specific cell types and tissue are observed.

More Connective Tissue in the SA node of Older Hearts

• Images comparing connective tissue in young and old hearts are detailed, showing how age affects the tissues and cells of the SA node.

Older hearts have slower SA Node conduction velocities

• Older hearts exhibit slower rates of conduction in the SA node. This analysis uses statistical measures relating the speed and age.

Intrinsic Conduction System - The AV node

• The AV node is located in the inferior interatrial septal wall, delaying impulses for approximately 0.1 seconds
• The node's smaller fiber diameter results in fewer gap junctions, allowing for complete atrial contraction before ventricular contraction. Its inherent rate is 50 beats per minute.

Intrinsic Conduction System - The AV node and Bundle Branches

• The AV bundle (bundle of His) is the sole electrical connection between atria and ventricles.
• Atria and ventricles are not directly connected through gap junctions.
• The right and left bundle branches carry impulses towards the heart's apex.

Intrinsic Conduction System – Purkinje Fibers

• The subendocardial network (Purkinje fibers) completes the conduction pathway. It extends from the interventricular septum to the ventricular walls.
• The left side has a more elaborate arrangement of these fibers. Ventricular contraction begins at the apex and spreads towards the atria.
• Ventricular contraction takes around 0.22 seconds, from initiation in the SA node.

Intrinsic Conduction System

• This system, a network of specialized tissues, initiates and conducts the heartbeat.
• It has parts, including the SA node, internodal pathways, and AV node.

Conducting System – Coordinated units

• Autorhythmic cells in the different locations of the heart initiate and control the heart rate. Gap junctions link cardiac cells.
• The SA node is the fastest depolarizing cell, acting as the pacemaker and setting the heartbeat.

Different Cardiac Cells Have Different Action Potentials

• Pacemaker cells have unstable resting potentials and spontaneous depolarization, unlike contractile cells that have steady resting membrane potentials.
• Contractile cells demonstrate rapid and sharp depolarization, a feature not seen in pacemaker cells.

Action Potentials of Contractile Cardiac Muscle Cells

• Depolarization (Step 1) is driven by fast voltage-gated Na+ channels, which causes a positive feedback influx of Na+, initiating the rising phase of the action potential.
• Depolarization (Step 2) by Na⁺ also gradually opens slow Ca²⁺ channels, maintaining the plateau phase as Na⁺ channels close.
• Repolarization (Step 3) is achieved by K+ channels opening, causing efflux of K⁺ to reduce the intracellular positive charge, and returning the membrane potential to its resting state.

Contractile Cardiac vs Contractile Skeletal Muscle

• Unlike skeletal muscle, cardiac muscle has a longer action potential and contraction. This longer refractory period is essential for preventing sustained contractions (tetany).
• The longer action potential and contraction in cardiac muscle ensure efficient ejection of blood.

Cardiomyocyte – Action Potential vs. Force Generated

• Action potential duration in cardiomyocytes doesn’t directly correlate to tension generation, which is dependent on the plateau phase.

Skeletal Muscle - Can Develop Tension in Different Ways

• Skeletal muscle can develop tension in various ways through different frequencies of stimulation. Higher frequencies lead to greater tension accumulation.

Cardiac Muscle - Develops Tension in Only One Way

• Cardiac muscle generates tension only when a single stimulus occurs. It is unable to generate greater tension with further stimuli because of the long refractory period.

Absolute and Relative Refractory Periods

• The absolute refractory period prevents subsequent stimulation of a heart cell that has just gone through an action potential.
• The relative refractory period adds to this, preventing premature contractions.

Cardiac AP Phases

• The different phases of the cardiac action potential are described and illustrated. Each has unique characteristics which are crucial for the efficient functioning of the heart's electrical activity.

Inward and Outward Ionic Currents

• Electrical signals in cardiovascular physiology are understood in terms of ions flowing in and out of cells in controlled ways. The names and directions of ion flow through their associated channels clarify the processes within the cell membranes.
• The Na+/K+ ATPase channel's ongoing activity helps establish the typical resting potential for the cell and subsequent action potentials.

Myocardial Action Potential – Sequence of Permeability to Na+, Ca2+, and K+

• Phases 0–4 of the myocardial action potential detail the ion currents within cells through specialized membrane channels. Each of these phases is crucial for the efficient conduction and contraction of the heart.

Cardiomyocyte – Relaxation

• The cessation of the plateau phase of the action potential initiates the relaxation phase of cardiomyocytes. Ion current direction and pump activity are key for the process of relaxation.

Intrinsic Conduction System

• Pacemaker activity is a function of unstable resting membrane potentials (pacemaker potentials), which are unique parts of these cells' action potentials.

Intrinsic Conduction System –Activity in PACEMAKER Cells

• Pacemaker potentials are seen as slow depolarizations in cardiomyocytes. When reaching a threshold, depolarization and repolarization sequences are initiated by various ions' movements.

SA Node Sinoatrial Node Action Potential

• Depolarization in SA node cells is relatively slow compared to other cardiac cells. It gradually reaches the threshold and initiates the action potential. Phases in the SA node action potential are described.

Phases in SA Node AP

• The different phases in the SA node action potential (Phases 0, 1, 2, 3, and 4) are outlined, describing the ion currents and accompanying membrane potential changes during the process.

Ion Currents During the SA Node Action Potential

• The action potential phases (0-4) in the SA node are detailed, identifying the corresponding ionic currents (e.g., ik, iCa_L, i_f).

Fast Response and Slow Response

• The graphs show the differences in the action potentials. The descriptions detail the voltage curves for fast and slow responses.

Explore cardiac action potentials phases (0-4), ionic currents, and the role of the sodium-calcium exchanger (NCX). Understand the heart's anatomy, the fibrous skeleton, and the sinoatrial (SA) node significance.