Cellular physiology of the Heart Flashcards
What is SERCA
Sarcoplasmic/endoplasmic reticulum calcium ATPase pump that plays a role in cardiac muscle function by regulating calcium reuptake into the SR after a contraction
A new compound is developed that decreases the activity of the SERCA in a cardio myocyte. What will the impact be on overall function?
Decreased SERCA activity would:
1) impair Calcium reuptake: prolonged muscle relaxation - diastolic dysfunction
2) reduce calcium release for contraction causing weaker heartbeats - negative inotropy
3) over time lead to heart failure due to decreased cardiac output and hyertrophy and risk of arrhythmias due ot calcium imbalance
where does most of the calcium that the cytoplasm come from?
The SR - Sarcoplasmic reticulum
L-type Ca+2 VGC allows a little calcium into the cell, but the MAIN action is?
opening the ryanodine receptor in the SR
What are 3 differences between Skeletal vs Cardiac myocytes?
No tetanic contraction (sustained muscle contraction) in cardiac due to long electrical refractory period
syncytium
cardiac cells have 1 single nucleus and lots of mitochondria
what is the role of T-tubules in cardiac muscle?
they exist in both cardiac and skeletal but have a much less critical role in cardiac where they are larger but fewer.
Cardiac cells rely more on calcium influx where the T-tubules are more integral for calcium release from the SR
what generates the force required for contraction in both skeletal and cardiac muscle?
striated, actin-myosin overlap
the overlap of actin (thin filaments) and mysoin (thick filaments) leads to cross-bridge cycling during contraction
If a muscle (cardiac or skeletal) is too stretched or too compressed, the force production decreases, why? What relationship is this?
Parabolic isometric lenght-tension relationship
there is an optimal muscle length (sarcomere length) where the overlap b/t actin and myosin is ideal and generates the greatest force
when does peak isometric force occur in both skeletal and cardiac muscle?
when the muscle is at its optimum passive resting lenght. this is the point when actin-myosin overlap is ideal
what is the purpose of T-tubules in both cardiac and skeletal muscles?
help propagate action potentials deep into the muscle fibers, to make sure the excitation reaches the myofilaments for synchronized contraction
Proper regulation of calcium is critical for the contraction-relaxation cycle. What regulates this in both skeletal and cardiac muscle?
Ca+2 ATPase pumps in SR.
they actively transport calcium back into SR after a contraction, reducing intracellular calcium levels and allowing muscle relaxation
why can cardiac myocytes not undergo tetanic contraction?
long electrical refractory period that prevents another AP ensuring the full relaxation between beats and avoid dangerous sustained contraction
what does syncytium in cardiac myocytes mean?
cardiac muscle cells function as a syncytium, meaning the cells are interconnected through branches and intercalated disks. makes the heart function as a unified organ
how are adjacent cardio myocytes connected to eachother?
gap junctions cross the intercalated disks (syncytium)
4 major types of APs in the heart?
1 and 2. myocyte AP - atrial and ventricular
3. purkinje cells AP (almost the same as ventricular but unstable)
4. automatic cell APs
what are all 4 phases between cell types for APs?
phase 4 - resting membrane potential
phase 0 - rapid depolarization phase (upstroke)
phase 1 and 2: prolonged depolarizatio/plateau phase
phase 3 - repolarization
what are the similarities and differences between Atrial and ventricular APs?
both have distinct phases of depolarization, plateau, and repolarization, but atrial APs are shorter allowing for faster contraction cycles
what gives Purkinje cell APs the ability to spontaneously generate action potentials in abnormal conditions?
they are similar to ventricular Aps but with a slight unstable phase 4 (resting membrane potential)
what cell type APs sets the heart rate through automatic, rhythmic action potentials?
automatic cell APs: pacemaker cells (SA and AV nodes) have unstable phase 4 and depolarize spontaneously due to funny current (If)
Do action potentials directly or indirectly bring about contraction and generate force?
indirectly
they are electrical events, they are NOT measures of contraction and not force generation
what are the mechanisms that increase cytosolic calcium?
calcium spark: when a Ca VGC opens a small amount of Ca release from ryanodine receptor on SR
Increases cytosolic Ca in a myocyte due to summation of all the sparks
What are the mechanisms that decrease cytosolic calcium? (calcium sequestered by?)
- SERCA : pumps Ca into SR by a mediator phospholamban (phosphorylation of phospholamban -> increased SERCA activity)
- sarcolemma calcium ATPase
- sodium calcium exchanger (2 sodium in 1 Ca out)
what is the impact of the sympathetic nervous system stimulation?
SNS beta-1 receptors -> increased cAMP
phosphorylation of:
- phospholamban
-troponin (down calcium affinity)
- L-type Calcium VGC (increase entry of Ca)
what triggers a calcium influx?
Action potentials
How do action potentials trigger calcium influx?
trigger the opening of L-type 1, 4 dihydropyridine (DHP) Ca2+ channels allowing Ca2+ to enter the cell from the extracellular space
What stimulates calcium release from the SR?
Calcium induced calcium release (CICR)
influx of calcium through these channels stimulat
What is an Calcium induced calcium release (CICR)?
influx of calcium through these channels stimulates calcium release from SR through calcium release channels, causing a calcium spark.
this amplification of calcium levels initiates a muscle contraction
what modulates calcium influx through DHP channels? allowing for control over the inotropic state (force of contraction) of the cardiac cells
G protein-coupled receptor mechanisms.
what is the role of cAMP and beta-adrenergic receptors?
beta-adrenergic pathways via cAMP enhances contractility and speeds relaxation of cell by promoting faster Ca reuptake into SR
after a contraction, how is calcium removed?
after contraction calcium is returned to low levels between action potentials by
- calcium pumps (ATPase) in SR (SERCA pump) and plasma membrane (PMCA)
- secondary active transport (Na-CA exhanger (NCX) in plasma memebrane)
