Lecture Notes: Excitation-Contraction Coupling in Cardiomyocytes

Lecturer: Eric Strong, Strong Medicine
Topic: Cardiovascular System - Excitation-Contraction Coupling

Introduction

• Excitation-Contraction Coupling: Series of events linking electrical activation of cardiomyocyte cell membrane via an action potential to actin-myosin crossbridge cycling resulting in cell contraction.
• Plan: Discuss excitation and contraction individually, then link them together.

Excitation

Sarcolemma and T-tubules

• Sarcolemma: Cell membrane of cardiomyocyte.
  • Contains integral membrane proteins anchoring the cell to the extracellular matrix.
• T-tubules: Imaginations of cell membrane, contiguous with extracellular space.
  • Allow rapid spread of action potential into cardiomyocyte.
  • Provide increased surface area for ion channels and pumps (e.g., L-type calcium channels).

Sarcoplasmic Reticulum

• Function: Storage of calcium ions.
• Structure: Extensive network surrounding myofibrils.

Action Potential and Calcium Release

• Phase 2 (Plateau) of Cardiac Action Potential: Inward calcium flow via L-type channels balances outward potassium flow.
  • Initial calcium increase is not sufficient for contraction, but triggers more calcium release from sarcoplasmic reticulum via ryanodine receptors.
• Sympathetic Nervous System: Modulates calcium surge via beta receptors increasing conductance of L-type channels.

Contraction

Sarcomere

• Contractile Unit: Repeats along myofibrils.
• Proteins: Actin and myosin, arranged in striated patterns with light and dark bands.
  • Z Discs: Anchor thin filaments (actin, tropomyosin, troponin complex).
  • M Lines: Anchor thick filaments (myosin).

Cross-bridge Cycling

• Sliding Filament Model: Contraction occurs through actin-myosin cross bridging using ATP.
• Myosin Structure: Long tail and head with actin binding site.
• Troponin Complex: Troponin I (actin affinity), Troponin T (tropomyosin affinity), Troponin C (calcium affinity).

Process

• Calcium binds to troponin C, causing tropomyosin to unblock actin's binding site.
• Myosin heads bind to actin, cycling through flexed and relaxed states, fueled by ATP.
• Once calcium levels drop, tropomyosin re-blocks binding sites.

Relaxation

• Calcium Reuptake: Into sarcoplasmic reticulum via ATP-dependent pump (SERCA).
• Sympathetic Regulation: Protein kinase increases L-type calcium channel conductance, modulates troponin I, and inhibits phospholamban.
• Relaxation: Active process requiring energy; facilitated by autonomic nervous system.
• Calcium Removal: Via ATP-dependent pump and sodium-calcium exchanger.

Summary

• Excitation-contraction coupling links electrical excitation to actin-myosin cross-bridge cycling.
• Both contraction and relaxation are ATP-dependent.
• Key Factors: Calcium dynamics, autonomic nervous system, proteins including troponin and tropomyosin.

Conclusion

• Encouragement to share and subscribe for more educational content on cardiovascular and other medical topics.