Cellular physiology of the Heart Flashcards

1
Q

What is SERCA

A

Sarcoplasmic/endoplasmic reticulum calcium ATPase pump that plays a role in cardiac muscle function by regulating calcium reuptake into the SR after a contraction

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2
Q

A new compound is developed that decreases the activity of the SERCA in a cardio myocyte. What will the impact be on overall function?

A

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

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3
Q

where does most of the calcium that the cytoplasm come from?

A

The SR - Sarcoplasmic reticulum

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4
Q

L-type Ca+2 VGC allows a little calcium into the cell, but the MAIN action is?

A

opening the ryanodine receptor in the SR

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5
Q

What are 3 differences between Skeletal vs Cardiac myocytes?

A

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

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6
Q

what is the role of T-tubules in cardiac muscle?

A

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

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7
Q

what generates the force required for contraction in both skeletal and cardiac muscle?

A

striated, actin-myosin overlap

the overlap of actin (thin filaments) and mysoin (thick filaments) leads to cross-bridge cycling during contraction

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8
Q

If a muscle (cardiac or skeletal) is too stretched or too compressed, the force production decreases, why? What relationship is this?

A

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

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9
Q

when does peak isometric force occur in both skeletal and cardiac muscle?

A

when the muscle is at its optimum passive resting lenght. this is the point when actin-myosin overlap is ideal

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10
Q

what is the purpose of T-tubules in both cardiac and skeletal muscles?

A

help propagate action potentials deep into the muscle fibers, to make sure the excitation reaches the myofilaments for synchronized contraction

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11
Q

Proper regulation of calcium is critical for the contraction-relaxation cycle. What regulates this in both skeletal and cardiac muscle?

A

Ca+2 ATPase pumps in SR.

they actively transport calcium back into SR after a contraction, reducing intracellular calcium levels and allowing muscle relaxation

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12
Q

why can cardiac myocytes not undergo tetanic contraction?

A

long electrical refractory period that prevents another AP ensuring the full relaxation between beats and avoid dangerous sustained contraction

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13
Q

what does syncytium in cardiac myocytes mean?

A

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

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14
Q

how are adjacent cardio myocytes connected to eachother?

A

gap junctions cross the intercalated disks (syncytium)

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15
Q

4 major types of APs in the heart?

A

1 and 2. myocyte AP - atrial and ventricular
3. purkinje cells AP (almost the same as ventricular but unstable)
4. automatic cell APs

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16
Q

what are all 4 phases between cell types for APs?

A

phase 4 - resting membrane potential

phase 0 - rapid depolarization phase (upstroke)

phase 1 and 2: prolonged depolarizatio/plateau phase

phase 3 - repolarization

17
Q

what are the similarities and differences between Atrial and ventricular APs?

A

both have distinct phases of depolarization, plateau, and repolarization, but atrial APs are shorter allowing for faster contraction cycles

18
Q

what gives Purkinje cell APs the ability to spontaneously generate action potentials in abnormal conditions?

A

they are similar to ventricular Aps but with a slight unstable phase 4 (resting membrane potential)

19
Q

what cell type APs sets the heart rate through automatic, rhythmic action potentials?

A

automatic cell APs: pacemaker cells (SA and AV nodes) have unstable phase 4 and depolarize spontaneously due to funny current (If)

20
Q

Do action potentials directly or indirectly bring about contraction and generate force?

A

indirectly

they are electrical events, they are NOT measures of contraction and not force generation

21
Q

what are the mechanisms that increase cytosolic calcium?

A

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

22
Q

What are the mechanisms that decrease cytosolic calcium? (calcium sequestered by?)

A
  1. SERCA : pumps Ca into SR by a mediator phospholamban (phosphorylation of phospholamban -> increased SERCA activity)
  2. sarcolemma calcium ATPase
  3. sodium calcium exchanger (2 sodium in 1 Ca out)
23
Q

what is the impact of the sympathetic nervous system stimulation?

A

SNS beta-1 receptors -> increased cAMP
phosphorylation of:
- phospholamban
-troponin (down calcium affinity)
- L-type Calcium VGC (increase entry of Ca)

24
Q

what triggers a calcium influx?

A

Action potentials

25
Q

How do action potentials trigger calcium influx?

A

trigger the opening of L-type 1, 4 dihydropyridine (DHP) Ca2+ channels allowing Ca2+ to enter the cell from the extracellular space

26
Q

What stimulates calcium release from the SR?

A

Calcium induced calcium release (CICR)

influx of calcium through these channels stimulat

27
Q

What is an Calcium induced calcium release (CICR)?

A

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

28
Q

what modulates calcium influx through DHP channels? allowing for control over the inotropic state (force of contraction) of the cardiac cells

A

G protein-coupled receptor mechanisms.

29
Q

what is the role of cAMP and beta-adrenergic receptors?

A

beta-adrenergic pathways via cAMP enhances contractility and speeds relaxation of cell by promoting faster Ca reuptake into SR

30
Q

after a contraction, how is calcium removed?

A

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)

31
Q
A