Rhythmical Excitation of the Heart

Rhythmical Excitation of the Heart

Introduction

• The heart possesses a specialized system for rhythmic self-excitation and repetitive contraction.
• Normal heart contraction rate: ~70 contractions per minute.
• Approximate number of contractions:
  • ~100,000 contractions per day.
  • ~3,000,000,000 contractions per lifetime.
• The heart generates electrical impulses to initiate rhythmical contraction and conducts these impulses rapidly throughout the heart.

Atrial and Ventricular Contraction

• Atria contract about 1/6th of a second before ventricular contraction.
• This timing allows for filling of the ventricles before they pump blood out of the heart.
• The rhythmical and conductive system of the heart is susceptible to damage by heart disease, leading to bizarre rhythms or abnormal contraction sequences.

Excitatory & Conductive System

• Key components:
  • Sinoatrial (S-A) node (or Sinus node).
  • Atrioventricular (A-V) node.
  • A-V bundle (Bundle of His).
  • Internodal pathways.
  • Left and right bundle branches.

Sinus Node

• Located in the superior posterolateral wall of the right atrium, just below and lateral to the opening of the superior vena cava.
• Composed of specialized muscle fibers with almost no contractile filaments.
• Nodal fibers connect directly with atrial muscle fibers.
• Action potentials (APs) originating in the sinus node spread immediately into the atrial muscle wall.

Automatic Electrical Rhythmicity

• The conducting system has the capability of self-excitation, leading to automatic rhythmical discharge and contraction.
• The sinus node primarily controls the heart rate.

Mechanism of Sinus Nodal Rhythmicity

• "Resting membrane potential" of nodal fibers is less negative ($-55$ to $-60$ mV) compared to ventricular muscle ($-85$ to $-90$ mV).
• The resting membrane potential is a drifting potential due to leaky sodium/calcium ion channels.
• Self-excitation leads to automatic rhythmical discharge and contraction in the sinus node.

Cardiac Muscle Ion Channels

• Three main types of membrane ion channels:
  • Fast sodium channels.
  • Calcium channels (slow).
  • Potassium channels.
• These channels play important roles in causing voltage changes in action potentials.

Ion Channel Function in Ventricular Muscle

• Opening of fast sodium channels causes rapid upstroke spike of action potential (lasting a few 10,000ths of a second).
• Plateau phase is due to slow sodium-calcium channels (lasting ~0.3 seconds).
• Potassium channels allow outward diffusion, returning membrane potential to resting state.

Sinus Nodal Fiber Differences

• Less negativity ($-55$ mV vs $-90$ mV) compared to ventricular muscle fibers.
• Fast sodium channels are inactivated due to millivoltage, unlike in ventricular muscle fibers.
• Slow sodium-calcium channels cause action potentials in the SA node.
• Atrial nodal action potential develops more slowly as a result.

AP in Sinus Nodal Fiber: Repolarization

• Return to the resting state occurs more slowly compared to ventricular muscle fiber.
• Potassium channels remain open for a few tenths of a second, resulting in excess negativity or hyperpolarization of the nodal fiber to $-55$ to $-60$ mV at the termination of the AP when the K^+ channels close.

AP in Sinus Nodal Fiber: Leaky Sodium Channels

• Leakiness of sodium channels causes self-excitation.
• Action potential begins at a less negative resting potential ($-55$ mV) because fast Na^+ channels are blocked or “inactivated”.
• High Na^+ ion concentration outside of nodal fibers with open channels results in Na^+ ions leaking into fiber and a slow rise in the resting potential in a positive direction.

Discharge of Sinus Node Fiber

• Influx of sodium ions through slow Na^+ channels.
• Calcium channels are activated, causing action potential.
• Self-excitation occurs.
• Potassium channels allow potassium to leave cell, causing hyperpolarization.
• Potassium channels begin closing.
• Fast sodium channels close, trapping Na inside.

AP in Ventricular Muscle Fiber

• Rising phase: fast sodium channels followed by slow calcium channels opening.
• Plateau phase: calcium-activated calcium release.
• Falling phase: potassium channels opening.

EC Coupling

• Action potential
• Ca^{2+} pump requires ATP
• calsequestrin
• Ca2+/Na+ exchanger (Ca^{2+} out / Na^+ in)
• Sequence of Events:
  1. AP moves along T-tubule.
  2. Activation of DHP receptors – voltage sensors that release a small amount of Ca into the fiber.
  3. Ca then binds to the ryanodine receptor which opens, releasing a large amount of Ca (CACR).
  4. Calcium is pumped (a) back into SR, and (b) back into T tubule.
  5. Contraction is terminated.

Internodal Pathways: Anatomy

• Action potentials generated in the sinus node spread outward in specialized bands of atrial fibers:
  • Anterior Interatrial Band (Bachman’s Bundle) goes through anterior wall of the atrium into the left atrium.
  • Anterior, Middle, and Posterior Internodal Pathways traverse the atria and terminate in the A-V node.

Internodal Pathways: Delay

• The internodal pathways have an inherent conduction delay (0.03 sec) of the cardiac impulse that allows time for the atria to empty blood into the ventricles before ventricular contraction begins.
• The A-V node and its adjacent conductive fibers delay the cardiac impulse transmission into the ventricles.

A-V Bundle Conduction

• There is one-way conduction through the A-V Bundle that prevents, except in abnormal states, the impulse from traveling backward from ventricles to atria.

A-V Node

• Located on the posterior wall of the right atrium.
• Fibers of the A-V bundle or Bundle of His penetrate the fibrous tissue between atria and ventricles (one way).
• Once into the ventricles, the distal portion of the A-V bundle divides into the left and right bundle branches located in the ventricular septum.

Organization of the A-V Node

• The numbers represent the interval of time from the origin of the impulse in the SA node.

Fibrous Tissue Separates A&V

• A fibrous barrier exists between the muscle tissue of the atria and the ventricles such that the A-V node and bundle system is the only means of impulse conduction between atria and ventricles.

Purkinje System: Location

• Purkinje fibers lead from the A-V node through the A-V bundle into the ventricles.

Purkinje Fibers: Anatomy

• Large diameter fibers.
• Have high permeability at the gap junctions.
• Transmit the AP 6x faster than the ventricular muscle after they penetrate the fibrous barrier
• 'Instantaneous' transmission of the AP through the ventricles.
• Penetrate 1/3 of way into ventricle wall and become continuous with muscle fibers.
• Contain very few myofibrils, so no contraction of the Purkinje Fibers themselves.
• Once impulse reaches end of Purkinje Fibers, transmitted thru ventricular muscle mass by muscle fibers.

Summary of the Spread of the Cardiac Impulse Through the Heart

• Transmission of the cardiac impulse through the heart, showing the time of appearance (in fractions of a second after initial appearance at the SA node) in different parts of the heart.

Sinus Node as Pacemaker

• Sinus node controls heartbeat because its rate of discharge is faster than that of other parts of the heart.
• SA is better than AV and PF for self-excitation.
  • Sinus Node rate is 60 – 80 times/min.
  • A-V Node rate is 40 – 60/min.
  • Purkinje Fibers rate is 15 – 40/min.

Ectopic Pacemakers

• A pacemaker elsewhere than the sinus node is called an ectopic pacemaker.
• Causes abnormal sequence of contraction and affects heart pumping.
  • Sinoatrial Block - Impulse from sinus node to heart is blocked
    • A-V node or bundle becomes pacemaker

Ectopic Pacemakers Continued

• A-V Block – impulse from atria to ventricles is blocked
  • Atria beat normally with sinus node impulse; Purkinje system in ventricles becomes pacemaker
• Stokes-Adams Syndrome – follows a sudden A-V block; impulses not conducted and a delay of 5 – 20 sec occurs before ventricles contract. Due to delay, patient may faint, can be life threatening.
  • Some part of Purkinje system, usually distal A-V node or bundle becomes the pacemaker.

ANS and the Heart

• Parasympathetics (CN X - Vagus)
  • are distributed mainly to the Sinus and A-V nodes, and to a lesser extent the muscle of the atria, little directly to the ventricular muscle
• Sympathetics (Sympathetic chain ganglia)
  • are distributed to all parts of the heart, with strong innervations to ventricles and other areas

Parasympathetics and the Heart

• Vagal stimulation releases acetylcholine, and it has two effects on the heart:
  1. Decreases rate and rhythm of Sinus node
     • Due to increasing the permeability to K+ so that the SA node becomes hyperpolarized
  2. Decreases the excitability of the A-V junctional fibers between atrial musculature and the A-V node slowing transmission of the cardiac impulse into the ventricles

Parasympathetics and the Heart Continued

• Weak to moderate vagal stimulation slows the rate of heart pumping
• Strong vagal stimulation can block signal transmission from sinus to A-V nodes (ex. A-V block * see Stokes – Adams Syndrome )
  • Causing ventricles to stop beating for 5 – 20 sec after which part of the Purkinje system (A-V bundle) establishes a rhythm of ventricular contraction ~ 15 – 40 bpm. This is called ventricular escape.

Sympathetics and the Heart

• Sympathetic stimulation releases norepinephrine and increases overall activity of the heart in three ways:
  1. Increases rate of sinus node discharge
  2. Increases rate of conduction and excitability in all portions of the heart
  3. Increases force of contraction in all cardiac muscle
     • Due to increased permeability of fibers to Na^+ and Ca^{++} ions

Mechanism of Sympathetic Effect

• Norepinephrine stimulates beta-1 adrenergic receptors which mediate HR
• Increases permeability of fiber membrane to Na and Ca
• In SA node, increase in permeability causes more positive resting potential and upward drift, causing more self-excitation
• Also eases excitation in AV node and AV bundles, decreasing conduction time