Muscle Structure & Function

Question 1

Discuss the types of troponins and tropomyosin in cardiac cells

Answer 1

• Troponin C: Ca binding
• Troponin I: Inhibitory, prevents interaction of myosin and actin (contains 2 PKA phosphorylation sites that are critical for adrenergic responsiveness of the heart, fine tunes contraction)
• Troponin T: Tropomyosin binder; . Developmental regulation of isoform expression (and perhaps pathological regulation).
• Tropomyosin: Only alpha isoform is in the heart

Question 2

Discuss cardiac muscle structure

Answer 2

• Composed of interconnected mono-nucleated cells imbedded in a weave of collagen.
• Much of the cell volume is occupied by mitochondria (85% myofibril & mitochondria).
• Cells are coupled both electrically and mechanically
• ATPase activity is slower than skeletal
  Myosin has 2 heavy chains and 4 light chains. Mostly beta heavy chain, 10% alpha heavy chain.

Question 3

Discuss Ca flow regulation in cardiac cells

Answer 3

• Depolarization opens L-type calcium channels leading to calcium influx.
• Calcium influx triggers more calcium release from the SR through the ryanodine receptors (CICR)
• Calcium binding to TN-C triggers contraction
• 70% Ca2+ is removed by the SR Ca2+ATPase (SERCA), 28% by Sarcolemma Na+ Ca2+ exchanger, 2% by PMCA and mitochondrial uniporter

Question 4

Describe the cross-bridge cycle

Answer 4

• In resting muscle, at low intercellular Ca, the TN-TM complex inhibits the actin-myosin combination
• An increase in the myoplasmic Ca, TN releases it’s inhibition, moving TM out of the actin groove, allowing myosin to bind.
• Myosin heads undergo a power-stroke, and myofilaments shorten.

Question 5

Understand the mechanisms of altering cross-bridge cycling in cardiac muscle

Answer 5

???

Question 6

To understand the length-tension relationship (Frank-starling) in cardiac muscle

Answer 6

When cardiac muscle is stimulated to contract at low resting lengths (low preload), the amount of active tension developed is small.

If you increase the muscle length (increased preload), the active tension developed dramatically increases, up to a certain point.

Molecular Mechanism:

• Extent of overlap (Lo = 2.2 μm), juuuuust right
• Changes in Calcium-Sensitivity – amount of calcium needed to generate a given force.
• Stretch sensitive ion channels (stretch and change intracellular Ca)

So, AN INCREASE IN PRE-LOAD LEADS TO AN INCREASE IN STROKE VOLUME.

Question 7

5. To identify sarcomeric changes associated with heart failure

Answer 7

CFH: Tn-T LC1 LC2 MHC actin

Translational changes: Sarcomeric proteins (upregulation of fetal proteins)
Changes in signaling proteins: Post-translational changes of sarcomeric proteins (Is there a “phosphofingerprint” of cardiac disease?)