Cardiac Muscle Physiology and Reflexes: Study Notes for Anatomy & Physiology

Cardiac Muscle

Overview of Cardiac Muscle Structure

Cardiac muscle is a specialized form of muscle tissue found only in the heart. It is responsible for pumping blood throughout the body and exhibits unique structural and functional properties compared to skeletal and smooth muscle.

• Cardiac myocytes (also called myocardial cells) are short, branched cells with usually a single nucleus.

• Cells are interconnected by intercalated disks containing desmosomes (mechanical linkage) and gap junctions (electrical coupling).

• Cardiac muscle is striated and contains sarcomeres with thick (myosin) and thin (actin) filaments.

• Compared to skeletal muscle, cardiac muscle has less abundant but larger T-tubules and smaller amounts of sarcoplasmic reticulum (SR).

• Cardiac muscle relies on extracellular Ca2+ for contraction and has abundant mitochondria (about 1/3 of cell volume) for oxidative metabolism.

Example: Cardiac muscle cells can contract nearly 3 billion times over an average human lifespan.

Contractile vs. Autorhythmic Cells

Cardiac tissue contains two main types of cells: contractile cells and autorhythmic (pacemaker) cells.

• Contractile cells: Make up the majority of the myocardium and are responsible for generating force during heartbeats.

• Autorhythmic cells: Comprise about 1% of myocardial cells; they do not contract but generate and conduct action potentials spontaneously. Located primarily in the sinoatrial (SA) node and atrioventricular (AV) node.

Key Point: Contraction in cardiac muscle is not initiated by neurons but by autorhythmic cells that set the heart's pace.

Action Potentials in Cardiac Muscle

Cardiac muscle cells exhibit unique action potentials that differ between contractile and autorhythmic cells.

Autorhythmic Myocardial Cells

• Have an unstable resting membrane potential (~ -60 mV).

• HCN channels (hyperpolarization-activated cyclic nucleotide-gated channels) open at -60 mV, allowing Na+ influx and gradual depolarization.

• As threshold is approached, T-type Ca2+ channels open, further depolarizing the cell.

• At threshold, L-type Ca2+ channels open, causing a rapid depolarizing spike.

• Repolarization occurs as L-type Ca2+ channels close and K+ channels open.

Equation:

$I_{f} = g_{HCN}(V) \times (E_{Na} - V)$

(Additional info: This equation represents the "funny current" through HCN channels, contributing to pacemaker activity.)

Contractile Myocardial Cells

• Action potential is triggered by depolarization from adjacent cells via gap junctions.

• Phase 0: Rapid depolarization due to opening of voltage-gated Na+ channels.

• Phase 1: Brief repolarization as fast K+ channels open.

• Phase 2: Plateau phase due to slow opening of L-type Ca2+ channels and closing of fast K+ channels.

• Phase 3: Repolarization as Ca2+ channels close and slow K+ channels open.

• Phase 4: Return to resting potential.

Equation:

$AP_{cardiac} = \text{Phase 0} + \text{Phase 1} + \text{Phase 2} + \text{Phase 3} + \text{Phase 4}$

Excitation-Contraction Coupling in Cardiac Muscle

Excitation-contraction coupling describes how an action potential leads to muscle contraction.

• In cardiac muscle, L-type Ca2+ channels (DHP receptors) are not mechanically linked to ryanodine receptors as in skeletal muscle.

• Entry of extracellular Ca2+ is necessary for Ca2+-induced Ca2+ release from the SR via ryanodine receptors (RyR).

• Summed Ca2+ sparks create a Ca2+ signal that binds to troponin, initiating contraction by removing tropomyosin inhibition of cross-bridge cycling.

Equation:

$\text{Ca}^{2+}_{influx} \rightarrow \text{RyR activation} \rightarrow \text{Ca}^{2+}_{release}$

Relaxation in Cardiac Muscle

Relaxation occurs when Ca2+ is removed from the cytosol, allowing the muscle to return to its resting state.

• Ca2+ is removed primarily by reuptake into the SR via the SERCA pump and by extrusion to the extracellular space.

• The SERCA pump is regulated by phospholamban (PLN):

  • Dephosphorylated PLN inhibits SERCA, slowing Ca2+ reuptake.

  • Phosphorylated PLN relieves inhibition, enhancing Ca2+ reuptake and contractility.

Equation:

$\text{SERCA activity} \propto \text{PLN phosphorylation}$

Modulation of Contractile Activity

Cardiac muscle can adjust the force of contraction through changes in intracellular Ca2+ concentration.

• Unlike skeletal muscle, cardiac muscle does not use summation or recruitment for force regulation.

• Increased cytosolic Ca2+ activates more troponin complexes, leading to increased cross-bridge formation and force.

• Cardiac muscle exhibits graded single twitch contractions depending on Ca2+ availability.

Length-Tension Relationship in Cardiac Muscle

The force generated by cardiac muscle depends on the degree of stretch (preload) of the sarcomere.

• A slightly stretched sarcomere increases Ca2+ sensitivity and probability of cross-bridge cycling.

• Stretched sarcomeres may also increase Ca2+ influx from extracellular space, enhancing contraction.

Modulation of Conduction and Contraction by the Autonomic Nervous System

The heart is innervated by the autonomic nervous system, which modulates both conduction and contractility.

• Sympathetic stimulation: Increases heart rate, conduction velocity, and contractility via norepinephrine and epinephrine.

• Parasympathetic stimulation: Decreases heart rate and conduction via acetylcholine.

Mechanisms of Sympathetic Modulation:

• Phosphorylation of L-type Ca2+ channels increases Ca2+ conductance during action potentials.

• Phosphorylation of RyR enhances Ca2+ release from the SR.

• Increased rate of myosin ATPase accelerates cross-bridge cycling.

• Phosphorylation of PLN increases speed of Ca2+ reuptake, enhancing Ca2+ storage.

Reflexes: Crossed Extensor Reflex

Overview of Withdrawal and Crossed Extensor Reflexes

Reflexes are automatic, rapid responses to stimuli that help protect the body and maintain posture. The withdrawal reflex pulls a limb away from a painful stimulus, while the crossed extensor reflex coordinates movement in the opposite limb to maintain balance.

• Painful stimulus activates nociceptors in the skin.

• Primary sensory neurons transmit the signal to the spinal cord.

• Interneurons activate alpha motor neurons to contract flexors and inhibit extensors in the affected limb (withdrawal reflex).

• Simultaneously, extensors are activated and flexors inhibited in the opposite limb (crossed extensor reflex) to support body weight.

Reflex Component	Affected Limb	Opposite Limb
Painful stimulus	Activates nociceptors	-
Flexor muscles	Contract (withdrawal)	Inhibited
Extensor muscles	Inhibited	Contract (support)
Alpha motor neurons	Activated for flexors	Activated for extensors

Example: Stepping on a sharp object causes you to lift your foot (withdrawal reflex) while your other leg stiffens to support your weight (crossed extensor reflex).

Additional info: Reflexes are essential for rapid protective responses and postural adjustments, and are integrated at the level of the spinal cord.