Lecture 4: Cardiac Muscle & Electrical Activity I

Lecture 4: Cardiac Muscle & Electrical Activity I

• The cardiovascular system has three main components: heart, blood vessels, and blood.
• The heart is a muscular pump that creates pressure to push blood through blood vessels.
• Blood vessels are conduits that allow blood flow from the heart to cells and back to the heart (e.g., arteries, arterioles, capillaries, venules, veins).
• Blood is the fluid carried through the system.
• The heart is located in the thoracic cavity, with the diaphragm separating it from the abdominal cavity.
• The heart weighs approximately 250-350 grams and is roughly the size of a fist.

Pulmonary and Systemic Circulations

• Pulmonary capillaries involve deoxygenated blood entering the lungs.
• Oxygen diffuses from tissues into the blood in the lungs.
• Blood leaving the lungs is oxygenated.
• Systemic capillaries involve oxygenated blood entering tissues.
• Oxygen diffuses from the blood into tissues.
• Blood leaving tissues is deoxygenated.

Cardiac Muscle

• Cardiac muscle cells contain actin and myosin arranged in sarcomeres, similar to skeletal muscle cells.
• Cardiac muscle cells contract via sliding filament mechanism.
• Myocardial cells are short, branched, and connect to neighboring cells creating a complex network.
• Adjacent myocardial cells are joined by intercalated discs containing gap junctions.

Myocardial Cells

• Gap junctions are fluid-filled channels allowing action potentials to spread rapidly from cell to cell, making the myocardial cells simultaneously contract.
• Cardiac muscle is a syncytium.
• The property is "all or nothing".

Cardiac Muscle Contraction

• Skeletal muscle contraction requires external stimulation by somatic motor nerves, while cardiac muscle contraction is triggered by specialized noncontractile myocardial cells, also known as autorhythmic cells or pacemaker cells.
• Cell membranes spontaneously depolarize to generate action potentials that spread to surrounding contractile myocardial cells.

Sinoatrial Node

• Autorhythmic cells are concentrated in the sinoatrial (SA) node in the right atrium near the superior vena cava opening.
• Spontaneous depolarizations in the SA node spread to surrounding myocardial cells, triggering contractions.
• Atrial myocardial cells contract first, followed by a pause, then the Ventricular myocardial cells.
• Atrial and ventricular syncytium complete the process.

Cardiac Conduction System

• Spontaneous action potentials (APs) generated by the SA node spread through the atrial contractile cells.
• The APs then spread to the ventricles through the cardiac conduction system.

Atrial Conduction

• Impulses travel down atrial fibres at a rate of 1 m/sec.
• Specialized fibres like Bachmann's bundle conduct the impulse from the right into the left atrium.
• Impulses continue to the AV node.

Atrioventricular Conduction

• The AV node is located at the base of the right atrium near the interatrial septum.
• It is the only conduction pathway from atria to ventricles.
• Conduction velocity slows to 0.05 m/sec, causing a delay between atrial and ventricular excitation.
• The delay allows optimal ventricular filling during atrial contraction.

Ventricular Conduction

• The AV node conducts to the bundle of His, which branches into Purkinje fibers that conduct the impulse into ventricles.
• Purkinje fibres have a conduction velocity of 1-4 m/sec, due to their larger cell size (80 μM) compared to myocytes (15 μM).

Autorhythmic Cells

• Location:
• 1. Sinoatrial (SA) node in right atrium; most important location, APs spread to entire cardiac tissue (70-80 APs/min).
• 2. Atrioventricular (AV) node in the right atrium; generated if SA node is destroyed, APs generated (40-60 APs/min).
• 3. Pacemaker cells also in Purkinje fibers (30-40 AP/min). SA node APs normally inhibit autorhythmic activity in these cells.

Cardiac Action Potentials

• Two types of action potentials in cardiac tissue: fast response and slow response.
• Fast response is in atrial and ventricular myocytes (conductive or contractile cells).
• Slow response is in autorhythmic cells in the SA and AV nodes.

Action Potentials

• The Phases: Phase 0 (Upstroke), Phase 1 (Early repolarization), Phase 2 (Plateau), Phase 3 (Repolarization), and Phase 4 (Final Repolarization).
• ERP: Effective Refractory Period
• RRP: Relative Refractory Period

Myocardial Contractile Cells

• AP arrival opens voltage-gated Na+ channels, causing rapid depolarization.
• Voltage-gated Ca2+ channels open more slowly, prolonging depolarization.
• At +20 mV, Na+ channels close and K+ channels open, initiating repolarization.
• Slow inward Ca2+ diffusion balances the outward K+ diffusion, forming plateau phase.
• Ca2+ channels close and K+ channels complete repolarization.

Myocardial Cell Contraction

• Extracellular Ca2+ movement during depolarization opens Ca2+ channels on the sarcoplasmic reticulum.
• Increased intracellular [Ca2+] triggers contraction in an identical manner as skeletal muscle.
• Ca2+ is transported out of the cell during repolarization, leading to relaxation.

Excitation-Contraction Coupling

• Depolarization current spreads through gap junctions to contractile cells, allowing action potentials to travel along the plasma membrane and T-tubules.
• Ca2+ channels open in the plasma membrane and sarcoplasmic reticulum.
• Ca2+ induces Ca2+ release from the sarcoplasmic reticulum, causing exposure of myosin-binding sites.
• Crossbridge cycle begins, causing muscle contraction.
• Ca2+ is actively transported back into the sarcoplasmic reticulum and extracellular fluid, causing tropomyosin to block the myosin-binding sites, leading to muscle relaxation.

Cardiac Muscle Contraction

• Electrical current travels through the intercalated discs, connecting cells, and causing coordinated contraction.

Skeletal Muscle Contraction

• AP in skeletal muscle cell is fast (20 msec) and has a no-plateau phase.
• Repolarization occurs before contraction begins.
• The cell's responsiveness means further stimulation can occur during contraction, producing phenomena like summation and tetanus.

Myocardial Cell Contraction

• Myocardial cell AP duration (250 msec) is much longer than that of a skeletal muscle cell (20 msec).
• Plateau phase contributes to myocardial cell refractoriness.
• Summation of contraction and tetanus are prevented due to the long refractory periods of cardiac muscle cells.

Ca2+ Channels

• Cardiac muscle has various Ca2+ channels, but L-type Ca2+ channels (long-lasting) dominate.
• Opening these channels increases Ca2+ conductance due to their large concentration gradient.
• Ca2+ influx strengthens contraction.

In the Clinic

• Ca2+ channel antagonists (e.g., verapamil, diltiazem) decrease AP duration and contractility.