Physiology of skeletal muscle contraction Flashcards
What binds to troponin C in skeletal muscles?
4 Ca2+
What binds to troponin C in the heart muscle?
3 Ca2+
What happens to troponin after calcium binds?
Changes conformation
What does a conformational change in troponin (TnC) lead to?
Shuts off TnI
tropomyosin-troponin leaves F-actin groove
Unmasks the myosin binding site on actin
What happens to the next myosin that binds?
Next myosin head makes cross bridges (cycling) to actin
Myosin breaks down ATP
Myosin pulls thin filaments
What is total TnI used as a marker of?
Total muscle breakdown
What is cardiac TnI used as a marker of?
Myocardial infarction
What is cross bridge cycling?
Molecular cycle of actin-myosin interaction
Mechanism of contraction at a molecular level
What does contraction through cross bridge cycling depend on?
Binding of myosin heads to thin filaments (actin) at specific binding sites
Describe the resting state of a sarcomere
Myosin heads are blocked from binding to actin by tropomyosin, which occupies the specific binding sites ( F actin double helical groove)
What can increase the force generated?
Increased overlap of thick and thin filaments
When does the greatest force generation occur?
When sarcomere is at optimal length
Describe the process of cross bridge cycling in terms of te 4 reactions
Myosin releases actin
Myosin head cleaves ATP
Myosin binds actin
Power stroke
Where is creatine found?
Muscle fibres
What is creatine phosphorylated to?
Creatine phosphate
How is energy stored in muscle?
Stored as creatine phosphate in muscle fibres
Describe what happens to ATP during cross bridge cycling
ATP is hydrolysed to ADP + Pi , creatine phosphate donates high energy phosphate to ADP restoring it to ATP
How are ATP levels in muscle kept stable?
Buffering and regeneration
Which enzyme catalyses the reaction of ATP during cross bridge cycling?
Creatine kinase or Creatine phosphokinase (CK, CPK) in both directions
What is creatine?
Small molecule that accepts high energy phosphate bonds from ATP
What is plasma creatine phosphokinase a marker of?
Muscle destruction
What is creatinine a diagnostic marker of?
Kidney function
What is creatinine?
Breakdown product of creatine
What are the two calcium gradients?
Extracellular vs cytosolic free calcium
SR vs cytosolic free calcium
What provides most of the calcium?
Efflux of calcium from the sarcoplasmic reticulum to cytoplasm
What does calcium entering the cell from the outside provide?
Only a small fraction of the calcium needed for muscle contraction
What does calcium trigger?
Contraction
Which neurotransmitter leads to depolarisation?
ACh
What does depolarisation cause?
Increase in calcium
Name the receptor where there is a net inward current
Active nicotinic AChR
How does depolarisation spread?
Through T tubules
What do local action potentials trigger?
Ca2+ efflux from terminal cisternae across sarcoplasmic reticulum into the fibre cytoplasm
Where is the ryanodine receptor found?
In the sarcoplasmic reticulum
What does the ryanodine receptor do?
Releases Ca2+ from SR
What is the ryanodine receptor triggered by?
Voltage sensor on Ca2+ channel
Where is SERCA found?
In sarcoplasmic reticulum
What does SERCA stand for?
Smooth endoplasmic reticulum calcium ATPase