Myocardial Physiology
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- What is the source on NO in the heart?
- endothelial cells
- What forms scar tissue in the heart?
- collagen
- What are the roles of troponin I and troponin C?
- I=inhibits interaction between actin and myosin, C=binds Ca and thus allows interaction between actin and myosin
- Detail the Ca++ cycle from AP--> SR release
- AP--> depolarization --> small amount of Ca++ is released into the cell (trigger Ca) by Ca++ channel --> Ryaodine receptor (under cAMP-PKA control controls speed and strength of contraction) causes the mass release of Ca from SR -->
- Detail the removal of Ca++ from the cytoplasm into the SR.
- Ca is removed from troponin C by SR Ca ATPase and by Na/Ca exchanger and sarcolemma Ca ATPase pump
- What is the relationship between Ryanodine and phospholambin?
- In terms of the SR: ryanodine releases Ca, while phospholambin causes Ca uptake
- What is the biochemical basis for the effects of digitalis?
- It inhibits the Na/K ATPase pump, does this make more ATP available for Ca ATPase?
- What controls the uptake of Ca by the SR Ca ATPase?
- phospholamban, which when dephosphorylated inhibits Ca uptake, and when phosphorylated by a ß-adrenergic-cAMP mechanism it increases SR Ca ATPase uptake activity
- What happens upon phosphorylation of troponin I?
- It reduces the affinity of Ca to troponin C --> leading to muscle relaxation.
- What are three examples of the effects of phosphorylation on muscle activity?
- 1) Ryanodine receptor (phosphorylation --> increases contraction speed and strength), 2) Phospholamban (phosphoryaltion it increases the SR Ca ATPase uptake of Ca), 3) Troponin I (phosphorylation reduces Ca's affinity for Troponin C and thus enhances relaxation)
- What overall effect do ß-adrenergic mechanisms have on muscle?
- They enhance contraction and facilitate relaxation⬦ thus contractions are faster, stronger and relaxation is faster.
- What percentage of myocardium is occupied by mitochondria?
- 30%.. Thus, there is a high demand for oxygen⬦ there is not much capacity for oxygen debt⬦ without O2, heart muscle dies.
- How long can creatine phosphate maintain heart function?
- seconds
- What are the main substrates for producing energy for the heart?
- fatty acids, glucose, lactate, pyruvate and ketones. ⬦ FATTY ACIDS are the #1 source for energy, especially in the fasting state.
- What do ADP, NAD+, ß-adrenergic stimuli have in common?
- they stimulate metabolic patways
- What is the role of insulin?
- uptake of glucose by cells.
- In terms of metabolic substrates, what effect does an insulin deficiency, seen in diabetics, cause?
- a reliance on FAs, which may cause some pathologies.
- Why is a dependence on FAs, seen in diabetics a negative health factor?
- FAs require more oxygen per energy produced. Thus, it puts a larger strain on the heart.
- Can the heart use lactate as a metabolic substrate?
- yes, it converts it to pyruvate, which then enter the mitochondria.
- Does a small increase in ADP have a small effect on phosphorylation potential?
- No, it has a large effect.
- What two things regulate FA uptake?
- carrier system (FAT/CD36) and peroxisome proliferation-activator receptors (PPARs, which activate genes that are responsible for FA uptake and oxidation)
- Metabolically speaking, why is it FA metabolism is harder on the heart than glucose?
- 3 ATP/glucose⬦ and 2 ATP/FA⬦ thus, this puts a big strain on the heart function for diabetics
- What effect does cholinergic stimulation through muscarinic receptors have on cardiac function? Inhibitory or stimulatory?
- inhibitory
- In terms of contraction, what does tension equate to?
- tension = # of cross-bridges at any one time
- What are the three fundemental characteristics used to describe muscle contraction vs. energy consumption?
- Tension, velocity of contraction, and the extent of shortening during contraction⬦ Each component has its own energy cost associated with it. Thus, in a diseased state, concerns would be to lower tension (BP), lower speed of contraction, increase shortening, and decrease BPM.
- Which of the the three fundamental charactistics of muscle contraction have the most energy associated with it? (in fact it has a linear relationship with respect to energy)
- Tension (shortening has very little energy associated with it.)⬦ however, speed of contraction is also energetically costly.