Electrical-mechanical coupling

The Spark & The Squeeze - ECC Fundamentals

• Initiation: Depolarization opens voltage-gated L-type $Ca^{2+}$ channels in T-tubules.
• CICR: A small influx of extracellular $Ca^{2+}$ triggers ryanodine receptors (RyR2) on the sarcoplasmic reticulum (SR) to release a larger flood of intracellular $Ca^{2+}$.
  • This is Calcium-Induced Calcium-Release (CICR).
• Contraction: $Ca^{2+}$ binds Troponin C, moving tropomyosin, exposing actin-binding sites for myosin cross-bridging.
• Relaxation: Requires $Ca^{2+}$ removal via SERCA (back into SR) and Na+/Ca²⁺ exchanger (out of cell).

⭐ Unlike skeletal muscle, cardiac muscle contraction strength is directly proportional to the amount of $Ca^{2+}$ released and is critically dependent on extracellular $Ca^{2+}$ influx for CICR.

Calcium-Induced Calcium Release - The Key Player

• Phase 2 of the cardiac action potential initiates Excitation-Contraction (E-C) coupling.
• Depolarization propagates down T-tubules, activating voltage-gated L-type Ca²⁺ channels (dihydropyridine receptors).
• This allows a small, essential influx of "trigger" Ca²⁺ into the cardiomyocyte.
• This trigger Ca²⁺ binds to and opens Ryanodine Receptors (RyR2) on the sarcoplasmic reticulum (SR).
• This binding results in a large-scale release of Ca²⁺ from the SR into the cytosol.
• Increased cytosolic Ca²⁺ binds to Troponin C, displacing tropomyosin and enabling actin-myosin cross-bridge formation, leading to contraction.
• Relaxation is driven by Ca²⁺ removal:
  • SERCA pumps Ca²⁺ back into the SR.
  • Na⁺/Ca²⁺ exchanger (NCX) expels Ca²⁺ from the cell.

⭐ The force of cardiac muscle contraction is graded and directly proportional to the intracellular Ca²⁺ concentration, unlike the all-or-none contraction of skeletal muscle.

Cross-Bridge Cycling - The Power Stroke

• Initiation: ↑ intracellular $Ca^{2+}$ binds to Troponin C, moving tropomyosin and exposing myosin-binding sites on actin.
• Cross-Bridge Formation: High-energy myosin head (with ADP and $P_i$ bound) attaches to the actin filament.
• The Power Stroke:
  • Myosin releases ADP and $P_i$.
  • The myosin head pivots and bends, pulling the actin filament toward the M-line. This shortens the sarcomere.
• Detachment:
  • A new ATP molecule binds to the myosin head.
  • This binding reduces the affinity of myosin for actin, causing it to detach.
• Reactivation:
  • The myosin head hydrolyzes ATP to ADP and $P_i$ ($ATP \rightarrow ADP + P_i$).
  • This hydrolysis re-cocks the myosin head into its high-energy, "ready" position.

⭐ In rigor mortis, the absence of new ATP after death prevents myosin heads from detaching from actin. This results in a state of sustained muscle contraction and stiffness.

Myocardial Relaxation - The Big Chill

• SERCA2a Pump: The primary mechanism. Uses ATP to actively sequester $Ca^{2+}$ back into the sarcoplasmic reticulum (SR).
  • Phospholamban (PLN) acts as a brake on SERCA. Phosphorylation (e.g., by β-agonists) releases this brake, speeding up relaxation (positive lusitropy).
• Na⁺/Ca²⁺ Exchanger (NCX): A secondary route. Ejects one $Ca^{2+}$ ion out of the cell for every three $Na^{+}$ ions that enter.
• Result: Cytosolic $[Ca^{2+}]$ falls, causing $Ca^{2+}$ to detach from troponin C. This allows tropomyosin to re-cover myosin-binding sites on actin, leading to myofilament relaxation.

⭐ Positive Lusitropy: β-adrenergic stimulation phosphorylates phospholamban, removing its inhibitory effect on SERCA. This accelerates $Ca^{2+}$ reuptake into the SR, causing faster myocardial relaxation and allowing more time for diastolic filling.

High‑Yield Points - ⚡ Biggest Takeaways

• Excitation-contraction coupling links the myocyte action potential to muscle contraction.
• The action potential opens voltage-gated L-type Ca²⁺ channels in the T-tubules, causing Ca²⁺ influx.
• This influx triggers calcium-induced calcium release (CICR) from the sarcoplasmic reticulum via ryanodine receptors.
• The subsequent sharp ↑ in cytosolic [Ca²⁺] allows calcium to bind to troponin C.
• This binding uncovers myosin-binding sites on actin, initiating cross-bridge cycling and contraction.
• Relaxation requires Ca²⁺ reuptake into the SR by SERCA and extrusion by the Na⁺/Ca²⁺ exchanger.