Cellular Basis of Heart Failure Flashcards
What is the leading cause of death and the most common reason for hospitalization for those 65 yrs or older?
Heart failure
What is heart failure?
Hearts that cannot sustain an adequate cardiac output become breathless, have swollen feet and ankles,
Why does one become breathless from heart failure?
Because blood backs up from the left side of the heart into the lungs.
Why does one get swollen feet and ankles form heart failure?
Because blood backs up from the right side of the heart and promotes net filtration from systemic capillaries into the interstitial fluid.
Decreased contractility of the heart can be a consequence from?
Hypertrophy
What are 2 channels that could cause changes in intracellular calcium concentrations in cardiomyocytes?
- Cav1.2 L-type Ca2+ channel in the plasma membrane
2. Ca2+ release channel RYR2 in the SR
In hypertrophy that leads to heart failure, what is the underlying mechanism?
The Cav1.2 channels have difficulty activated the RYR2 channels through Ca2+-induced Calcium release
What is responsible for the impaired coupling between the Cav1.2 channels and the RYR2 channels?
- The spacing between the 2 channels
2. Depletion of calstabin 2
What is calstabin 2 responsible for?
Regulating the RYR2 channel
What is the physiological consequence of depleted calstabin 2?
The RYR2 channels become leaky and allows calcium to be continuously released.
Can changes in the expression of contractile proteins influence cardiomyocyte contractility?
Yes
What are the 2 isoforms of myosin heavy chains found in the heart?
alpha-MHC & beta-MHC
The speed of muscle shortening increases with the expression of?
alpha-MHC
In heart failure, expression of which myosin heavy chain isoform protein falls drastically from 35% to 2% relative to the total MHC concentration?
alpha-MHC
