Structure and Properties of Cardiac Muscle, and Mechanism of Cardiac Muscle Contraction

I. STRUCTURE OF CARDIAC MUSCLE

A. General Organisation

• Guyton and Hall Textbook of Medical Physiology

• Junqueira's Basic Histology, 17e

B. Microscopic (Histological) Structure

• Each cardiac myocyte is approximately 15-30 μm in diameter and 80 μm in length
• Cardiac muscle fibres consist of numerous cylindrical cells arranged end-to-end, unlike skeletal muscle which is a single multinucleated cell
• Histology: A Text and Atlas (Ross & Pawlina)

• Each cardiac muscle cell has a single, centrally placed nucleus (occasionally two)
• This is a key distinguishing feature from skeletal muscle, where multiple nuclei lie peripherally just beneath the sarcolemma
• The myofibrils separate to pass around the nucleus, forming a biconical juxtanuclear region rich in mitochondria, Golgi apparatus, lipofuscin granules, and glycogen
• Histology: A Text and Atlas

• Cardiac muscle is striated in the same manner as skeletal muscle, with typical myofibrils containing actin and myosin filaments arranged in A bands, I bands, H zones, and Z lines
• Each sarcomere (Z line to Z line) contains thick filaments (myosin) and thin filaments (actin + tropomyosin + troponin)
• Troponin C binds Ca²⁺; tropomyosin blocks myosin-binding sites when Ca²⁺ is absent
• Costanzo Physiology, 7e

• The most distinctive histological feature of cardiac muscle
• They appear as densely staining transverse bands crossing fibres in a linear or staircase (step-like) pattern in light microscopy
• Represent specialised cell-to-cell junctions between adjacent cardiac myocytes

• Fascia adherens: anchors actin filaments of the terminal sarcomere; analogous to the Z line
• Desmosomes (maculae adherentes): provide firm mechanical attachment; prevent pulling apart of cells during contraction
• Gap junctions: allow rapid ionic diffusion between cells; electrical resistance is extremely low, making cardiac muscle a functional syncytium

• Located at the Z line level in cardiac muscle (unlike skeletal muscle where they are at the A-I junction)
• Diameter is approximately 5 times greater than in skeletal muscle (volume 25 times greater)
• Open directly into the extracellular space, allowing extracellular Ca²⁺ to enter and be stored inside tubules
• Lined with mucopolysaccharides that are electronegatively charged and bind Ca²⁺
• Form dyads with the sarcoplasmic reticulum (not triads as in skeletal muscle)
• Guyton and Hall; Histology: A Text and Atlas

• Less well developed than in skeletal muscle
• Forms a dyadic structure with T-tubules (one SR terminal cisterna + one T-tubule)
• Contains ryanodine receptors (RyR2/Ca²⁺ release channels) on its membrane
• Stores Ca²⁺ that is released upon excitation
• Costanzo Physiology, 7e

• Extraordinarily abundant - occupy 25-35% of the cell volume
• Large mitochondria are densely packed between myofibrils, often extending the full length of a sarcomere, with closely packed cristae
• This reflects the heart's absolute dependence on aerobic metabolism (cardiac muscle is almost exclusively aerobic)
• Histology: A Text and Atlas

• Atrial cells contain specific secretory granules (0.3-0.4 μm) in the juxtanuclear cytoplasm
• Contain Atrial Natriuretic Factor (ANF) and Brain Natriuretic Factor (BNF)
• Both are diuretic hormones; inhibit renin and aldosterone secretion, and relax vascular smooth muscle
• BNF levels rise markedly in congestive heart failure (clinical marker)
• Histology: A Text and Atlas

II. PROPERTIES OF CARDIAC MUSCLE

1. Syncytial Property (Functional Syncytium)

• Because gap junctions at intercalated discs allow free ionic flow, the cardiac muscle acts as a functional syncytium
• Two syncytia exist: the atrial syncytium and the ventricular syncytium, separated by the fibrous skeleton of the heart (which electrically insulates them except at the AV bundle)
• When any part is stimulated, the action potential spreads through the entire syncytium → the heart contracts as one unit ("all-or-none" principle)
• Guyton and Hall

2. Rhythmicity (Automaticity)

• Cardiac muscle possesses inherent automaticity - it can generate action potentials spontaneously without external neural input
• Pacemaker cells (SA node) exhibit spontaneous phase 4 depolarisation due to the funny current (I_f) and generate rhythmic action potentials that drive the entire heart

3. Prolonged Action Potential and Refractory Period

• The cardiac action potential averages ~105 mV (resting: -85 mV → peak: +20 mV)
• It has a characteristic plateau lasting ~0.2-0.3 seconds, caused by:
  • Opening of L-type Ca²⁺ channels (slow calcium channels) - remain open for several tenths of a second
  • Reduced K⁺ permeability (K⁺ channels close during the plateau, unlike skeletal muscle)
• The long plateau makes ventricular contraction last 15 times longer than a skeletal muscle twitch
• The prolonged refractory period (lasting nearly the entire duration of contraction) prevents tetanic contraction - vital for the heart to relax and fill between beats
• Guyton and Hall

4. All-or-None Law

• A single cardiac muscle cell either contracts maximally or not at all; there is no partial contraction in response to sub-threshold stimuli

5. Frank-Starling Mechanism

• Within physiological limits, the force of contraction increases with the initial length of the muscle fibre (preload). Stretching of cardiac muscle increases sensitivity of troponin C to Ca²⁺ and increases cross-bridge formation.

6. Dependence on Extracellular Ca²⁺

• Unlike skeletal muscle (which relies almost entirely on intracellular SR calcium), cardiac muscle is critically dependent on extracellular Ca²⁺
• A heart placed in a calcium-free solution stops beating within ~1 minute
• Ca²⁺ enters through T-tubule L-type channels during the action potential plateau to trigger SR Ca²⁺ release
• Guyton and Hall; Harper's Illustrated Biochemistry, 32e

III. MECHANISM OF CARDIAC MUSCLE CONTRACTION

A. The Contractile Proteins

• Thick filaments: composed of myosin; globular heads have actin-binding sites and ATPase activity
• Thin filaments: three proteins - actin (two twisted strands with myosin-binding site), tropomyosin (runs along the actin groove and blocks myosin-binding site at rest), and troponin complex (troponin T - binds tropomyosin; troponin I - inhibits actin-myosin interaction; troponin C - binds Ca²⁺)
• Costanzo Physiology, 7e

B. Excitation-Contraction Coupling

• A cardiac action potential is initiated at the SA node and spreads across the sarcolemma
• Depolarisation travels into the cell interior via the T-tubules
• During phase 2 (plateau) of the action potential, L-type Ca²⁺ channels (dihydropyridine receptors, DHPRs) open, allowing Ca²⁺ to flow from extracellular fluid (ECF) into the cytoplasm (ICF)

• The Ca²⁺ entering through L-type channels acts as a "trigger Ca²⁺" - this small amount of Ca²⁺ alone is insufficient to initiate contraction
• It binds to ryanodine receptors (RyR2) on the SR membrane, triggering the release of a much larger amount of Ca²⁺ from SR stores
• This amplification mechanism is called Ca²⁺-induced Ca²⁺ release (CICR)
• The magnitude of Ca²⁺ release depends on: (a) amount of Ca²⁺ stored in SR and (b) the size of the inward Ca²⁺ current during the plateau
• Costanzo Physiology, 7e

• Intracellular Ca²⁺ concentration rises from ~0.1 μmol/L (resting) to ~1-10 μmol/L
• Ca²⁺ binds to troponin C (TnC), causing a conformational change in the troponin-tropomyosin complex
• Tropomyosin moves out of the myosin-binding groove on actin, exposing the active sites on actin

• Myosin heads bind to the exposed actin active sites, forming cross-bridges
• ATP hydrolysis drives a power stroke - the myosin head pivots, pulling the thin filament toward the centre of the sarcomere
• ADP + Pi are released; a new ATP binds to myosin, causing detachment of the cross-bridge
• The cycle repeats as long as Ca²⁺ occupies TnC binding sites → the Z lines move closer together → the sarcomere shortens → the entire cell shortens

• The magnitude of tension produced is directly proportional to the intracellular Ca²⁺ concentration
• This is why positive inotropes (e.g., digoxin, catecholamines) and negative inotropes (e.g., beta-blockers, Ca²⁺ channel blockers) act by altering intracellular Ca²⁺

C. Relaxation

• Ca²⁺ is reaccumulated into the SR via SERCA2 and extruded from the cell via sarcolemmal Ca²⁺-ATPase and NCX
• As Ca²⁺ falls, it dissociates from troponin C, tropomyosin returns to block actin, cross-bridge cycling stops, and the muscle relaxes
• Guyton and Hall; Costanzo Physiology, 7e

Summary Table: Cardiac Muscle vs. Skeletal Muscle

• Guyton and Hall Textbook of Medical Physiology (Guyton & Hall, 14e)
• Costanzo Physiology, 7th Edition
• Junqueira's Basic Histology: Text and Atlas, 17e
• Histology: A Text and Atlas with Correlated Cell and Molecular Biology (Ross & Pawlina)
• Harper's Illustrated Biochemistry, 32e

1. Action potential at SA node → spreads along sarcolemma
2. Depolarisation travels down T-tubules → L-type Ca²⁺ channels (DHPRs) open
3. Trigger Ca²⁺ enters from ECF
4. Trigger Ca²⁺ activates ryanodine receptors (RyR2) on the SR
5. Ca²⁺-induced Ca²⁺ release (CICR) - large Ca²⁺ floods cytoplasm
6. Ca²⁺ binds Troponin C → tropomyosin shifts → actin active sites exposed
7. Myosin cross-bridges form → power stroke (ATP) → sarcomere shortens → TENSION

• Ca²⁺ pumped back by SERCA2 (into SR), sarcolemmal Ca²⁺-ATPase, and Na⁺-Ca²⁺ exchanger (NCX)
• Ca²⁺ dissociates from TnC → tropomyosin re-blocks actin → cross-bridges detach → RELAXATION