G2iii: CVS Electrical Syllabus: Mechanical events of cardiac cycle

  • Excitation-Contraction-Coupling = the process whereby an AP is converted to a mechanical response
  • Calcium is the crucial mediator that couples electrical excitation to physical contraction

Contractile Elements

  • Myosin = thick filaments with globular heads contains myosin APTase
  • Actin = thin filaments

Regulatory Elements

  • Tropomyosin = lies between actin filaments blocking the Myosin Binding Site
  • Troponin = complex with 3 subunits sitting at regular intervals along actin strands
    • TnT = ties troponin complex to actin + myosin
    • TnI = inhibits activity of ATPase
    • TnC = binds calcium ions that regulate contraction
  • AP arrives at cell membrane → cell reaches threshold @ -40mV L-type Ca2+ channels open
  • Insufficient to trigger contraction of myofibrils
  • Amplified Ca2+ influx by the CALCIUM INDUCED CALCIUM RELEASE mechanism
  • Ca2+ binds RYANODINE RECEPTOR of myocyte SR
  • Mass Ca2+ release from SR
  • Ca2+ binds TnC on Actin Filaments
  • Displaces TROPOMYOSIN by conformational ∆
  • Exposes Myosin Binding Site
  • Hydrolysis of ATP on Myosin head
  • Induces CROSSBRIDGE FORMATION between Myosin Head & Actin

NB: strength of contraction proportional to no. of cross-bridges formed

  • This cycle repeats as Myosin travels further along actin molecules as long as there’s enough Ca2+ (to inhibit action of TnI) & ATP to drive crossbridge formation
  • L-type channels inactivate (100 msec)
  • ↓[Ca2+] = CICR trigger abolished
  • SERCA pumps on SR pump Ca2+ back into SR
  • Ca2+ dissociates from TnC
  • Tropomyosin inhibition is restored