Unit 3: Heart MicroAnatomy & Physiology

Overview of Cardiac Muscle

• Cardiac muscle shares similarities with skeletal muscle, particularly in terminology and structure.

Cardiac Muscle Cells

• Contractile cardiac muscle cells are known as cardiac monocytes or cardiac muscle fibers.

• Cardiac muscle is striated, indicating the presence of sarcomeres similar to those in skeletal muscle.

• Utilizes the sliding filament model for contraction, allowing oscillatory movements akin to a spring.

Structure and Function

• Fibers wrap around heart chambers, contracting to squeeze and reduce chamber volume, functioning as a pump.

• Although both skeletal and cardiac muscle cells have cylindrical or rectangular shapes, cardiac muscle fibers bifurcate or branch out, resulting in a less densely packed appearance under a microscope compared to skeletal muscle.

Intercellular Connections

• Adjacent cardiac muscle cells are interconnected to ensure coordinated contractions at the organ level.

• This interconnectivity is facilitated by intercalated discs, which consist of two types of junction proteins:

  • Desmosomes: Serve as physical connections (like a button) that couple adjacent cardiac myocytes while allowing flexibility during contraction and relaxation.

  • Gap junctions: Create electrical and chemical connections, enabling the sharing of ions and signaling molecules. This ensures that each cardiac myocyte can communicate with its neighbors electrically.

Syncytium Concept

• The extensive interconnections between cardiac myocytes allow them to function as a single unit, referred to as a syncytium.

• A syncytium is characterized by its highly integrated structure, allowing billions of cells to behave collectively.

• Visualization of syncytium can be demonstrated through experiments where cardiac myocytes are electrically stimulated, leading to synchronized contractions.

Implications of Loss of Syncytium

• If the electrical stimulation is interrupted, the cells begin to act independently, leading to erratic contractions.

• This could result in adjacent cells contracting in opposing directions, potentially causing a lack of coordinated heart function, which is critical for effective pumping.

Cardiac Muscle Contraction vs. Skeletal Muscle Contraction

• Similarities: At a molecular level, cardiac muscle contraction is similar to skeletal muscle contraction.

  • Both require an action potential to initiate contraction.

  • Calcium is crucial for muscle contraction in both types.

• Differences:

  • Innervation:

    • Skeletal muscle is innervated by alpha motor neurons.

    • Cardiac muscle is innervated by autonomic neurons and can generate its own action potentials (autorhythmic).

  • Function of Nervous System:

    • In cardiac muscle, the autonomic nervous system modulates the heart’s action rather than initiating it.

Action Potential and Calcium Cycling in Cardiac Muscle

• Excitation-Contraction Coupling:

  • Action potentials in cardiac myocytes result from depolarization.

  • Depolarization spreads along the plasma membrane to T-tubules.

  • L-Type Calcium Channels (LTCC):

    • Located in T-tubules, they open upon depolarization, allowing extracellular calcium to flow into the cytosol.

    • Close proximity to the sarcoplasmic reticulum (SR) facilitates calcium-induced calcium release.

• Ryanodine Receptors (RYR):

  • Calcium influx activates ryanodine receptors on the SR, releasing more calcium into the cytosol.

  • This increase in cytosolic calcium binds to troponin, moving tropomyosin out of the way for actin-myosin interaction, enabling contraction.

Calcium-Induced Calcium Release

• Mechanism:

  • Initial calcium entry via LTCC opens RYR, causing calcium from SR to flood into the cytoplasmic space.

  • Critical feature of cardiac muscle: requires extracellular calcium for contraction initiation, whereas skeletal muscle relies solely on calcium from the SR.

Regulation of Muscle Contraction Strength

• Strength of Contraction:

  • In cardiac muscle, contraction strength is determined by the amount of calcium released into the cytosol.

  • More calcium leads to more cross-bridge cycling, resulting in a stronger contraction.

  • This is visualized as shorter sarcomeres during increased contraction strength.

Relaxation Process in Cardiac Muscle

• Calcium Removal:

  • After contraction, calcium must be removed from the cytosol to allow the heart to relax for subsequent beats.

  • Majority of calcium returned to the SR through the Calcium ATPase (CIRCA) pump, which moves calcium against its gradient using ATP.

  • Additional calcium removal via the Sodium-Calcium Exchanger (NCX) and the Sodium-Potassium Pump (Na+/K+ Pump):

    • NCX allows sodium influx (down its gradient) while expelling calcium (against its gradient).

    • Na+/K+ Pump maintains low intracellular sodium levels necessary for NCX to function effectively.

Summary of Excitation-Contraction Coupling

• Process begins with action potential depolarizing cardiac myocytes, activating LTCC to increase calcium in the cytosol.

• This initiates contraction through calcium-induced calcium release and cross-bridge cycling between actin and myosin.

• Relaxation involves pumps like CIRCA and NCX returning calcium to the SR and the external fluid, ensuring muscle readiness for the next contraction.

Overview of Myocardium Cell Types

• The myocardium, primarily composed of contractile cells, is responsible for the heart's pumping action.

  • Contractile Cells: Make up about 99% of myocardial cells, responsible for heart contraction.

  • Noncontractile Cells (Pacemaker Cells): Comprise about 1% of myocardial cells, including cells from:

    • Sinoatrial (SA) node

    • Atrioventricular (AV) node

    • Purkinje fibers

  • Function: Noncontractile cells generate and propagate the electrical signals necessary for the contraction of contractile cells.

The Role of the SA Node

• The SA node, located in the right atrium, is known as the heart's natural pacemaker.

  • Pacemaker Activity: SA node can generate action potentials approximately 100 times per minute due to its autorhythmic cells.

• Mechanism of Action:

  • HCN Channels: Key to pacemaker activity; known as hyperpolarization-activated cyclic nucleotide channels.

    • Function: Open during hyperpolarization, allow sodium (Na+) influx, creating depolarization of the membrane potential known as the "funny current."

  • This depolarization is unlike skeletal muscle cells, where a stimulus is required for action potential generation.

Pacemaker Action Potential Characteristics

• Unique features of the pacemaker action potential include:

  • Lack of a stable resting membrane potential; it never flattens out.

  • Generated primarily through:

    • HCN channels

    • T-type and L-type calcium channels

    • Voltage-gated potassium channels

Spread of Depolarization

• The depolarization from the SA node spreads through the atria via internodal pathways:

  • Internodal Pathways: Extend between the SA node and AV node, facilitating communication.

• AV Node: Located between the right atrium and right ventricle; contains pacemaker cells that generate action potentials slower (60 times per minute).

  • AV node introduces a critical delay, allowing atrial contraction to finish before ventricular contraction begins.

Importance of AV Node Delay

• The delay created by the AV node is vital for the heart's mechanics:

  • It ensures that atrial contraction occurs before ventricular contraction, maintaining effective blood flow.

  • Prevents premature ventricular contractions, which could impede blood ejection from the heart.

Conduction Pathway in the Ventricles

• After passing through the AV node, the depolarization progresses as follows:

  • Through the interventricular septum via the AV bundle (Bundle of His)

  • Splits into the left and right bundle branches, descending to the apex of the heart.

  • Spreads into the Purkinje fibers, crucial for delivering depolarization signals to the ventricular contractile cells.

  • Contraction Sequence: Starts from the apex and moves towards the base of the heart to effectively eject blood into the arteries.

Features of Purkinje Fibers

• Purkinje fibers also exhibit autorhythmicity but at a much slower rate (20 times per minute).

  • Under normal operation, they follow the faster impulses of the SA node.

Functional Fail-safes of the Pacemaker System

• The heart has multiple pacemaker sites to provide redundancies:

  • If the SA node fails (e.g., due to heart damage), the AV node can take over but at a slower rhythm.

  • The Purkinje fibers can act if both the SA and AV nodes fail, though at a rate insufficient for most bodily demands.

Summary of Conductive Pathway Sequence

1. Depolarization begins in the SA node.

2. Spreads through internodal pathways to atria contractile cells.

3. Signal reaches the AV node and experiences a brief pause.

4. Progresses down the interventricular septum via the AV bundle and bundle branches.

5. Conducted through Purkinje fibers to ventricular contractile cells, facilitating contraction.