1 Cardiac Cell Biology Flashcards

1
Q

What similarities do cardiomyocytes have with skeletal?

A
  • basal lamina
  • striated
  • similar contractile proteins and mechanisms of contraction
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

How are cardiomyocytes different than skeletal?

A
  • involuntary
  • smaller with 1-2 central nuclei, intercalated discs, and branching
  • AEROBIC so more…
    • vasculature (seen with brown PECAM immunostaining)
    • mitochondria
    • myoglobin
    • lipid droplets
  • MB-creatine kinase and cTnl (skeletal has MM-CK)
  • CICR
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are two markers seen in the blood after and MI?

A

MB-creatine kinase and cTnl (cardiac troponin I) due to cardiomyocyte breakdown

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Describe a cardiomyote (identify EM structures on photo)

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is the ratio of thick:thin filaments in a cardiomyocyte?

A

6 thin per thick filament (like skeletal!)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is the function of intercalated discs?

A

They are sarcolemmal specializations that mediate cell-cell binding and enable cardiomyocytes to work as a single unit (producing rhythmic hearbeat)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Describe the layout of intercalated discs

A
  • “Staircase” layout
  • Transverse part (“modified Z line”;transmits force) consists of fascia adherens comprised of…
    • N-cadherins
    • Desmosomes
  • Lateral part (mediates cell-cell signaling)
    • Gap junctions (nexi)
    • Some desmosomes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Describe the excitation phase of cardiac contraction

A

**Bolded portions different from skeletal muscle

  • AP -> depolarization -> T tubules -> SR
  • L-type Cav1.2 channels -> calcium influx (CICR= Ca induced Ca release)
    • Do NOT directly bind RyR in SR
  • CICR -> ryanodine receptors in SR -> -> Ca
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Describe cardiac muscle contraction

A

**same as skeletal

  • Ca binds troponin C -> tropomyosin moves
  • ATP hydrolysis activates the myosin head
  • Myosin head binds actin
  • Power stroke: myosin pulls actin into A band
    • Sarcomere shortens= contraction
  • SERCA relaxes muscle as in skeletal
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

How does beta adrenergic stimulation affect the heart?

A

**Beta adrenergic receptors modulate the contractile response

cAMP increases -> protein kinases activated -> phosphorylation of L-type Ca channels and phospholamban

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are the effects of phosphorylation of L-type Ca channels and phospholamban?

A
  • Both caused by beta adrenergic modulation!
  • L-type Ca channels
    • Increased Ca uptake into myocyte (CICR)
    • Enhanced contractile force
  • Phospholamban
    • Permits Ca uptake by SR
    • Relaxation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are the sympathetic and parasympathetic innervations of the myocardium?

A
  • Symp= cervical ganglia
    • increased HR/”positive chronotropic”
  • Para= vagus
    • Acetylcholine -> muscarinic AchR -> inhibit adenlyate cyclase
    • decreased HR/”negative chronotropic” (via AchRs in SA node)
    • reduced contractile force/”negative inotropism” (beta adrenergic antagonist)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

How are atrial cardiomyocytes different than ventricular?

A

Atrial, SA, and AV nodal CMs are…

  • smaller with fewer striations than ventricular CMs
  • have granules with atrial natriuretic factor (ANF aka ANP)
  • ANF= pleiotropic (vasodilation, etc)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

How are bundle of His cardiomyocytes different than ventricular?

A

Bundle of His CMs= “purkinje” CMs

  • specialized for conduction
  • endothelin -> cardiac myocyte -> purkinje fiber
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is the most abundant cell type in the heart?

A

“Cardiac” fibroblasts

**but myocytes are much larger and occupy most of the heart’s volume

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Describe the timeline of a heart attack and the modifications afterwards

A
  • immediate myocyte death (MB-CK and cTnI released into bloodstream)
  • +15 hours= inflammation
  • +2-3 days= wound healing via cardiac fibroblasts (collagen deposition, leading to fibrosis)
  • +3-4 days= angiogenesis (enhanced by VEGF. FGF?)
  • Scar deposition by fibroblasts
17
Q

Can heart muscle regenerate?

A

“Maybe”…

Since 2000, we know that the myocardium naturally regenerates, but at a rate that’s far too low to restore function (turnover also decreases with age)

18
Q

Can skeletal myoblasts re-muscularize the injured heart?

A

Myoblasts= skeletal stem cells= satellite cells

**transplanted satellite cells cause arrhythmia and are therefore not therapeutically useful in the heart

19
Q

Are cardiac fibroblasts CM stem cells?

A

NO; fibroblasts respond to injury by making a scar which is permanent and cannot contract (bad!)

20
Q

Can pre-existing CMs proliferate to fix the heart?

A

Maybe… adult CM proliferation can be induced by inhibition of tumor suppressors and/or administration of pro-proliferative agents (e.g. Neuregulin)

21
Q

Can endogenous adult stem cells re-muscularize the damaged heart?

A

Apparently not… their existence is controversial

22
Q

What are c-kit+ cells?

A

Adult stem cells; autologous transplantation clinical trials underway to help myocardial repair after MI (results= “no harm done”)

**cKit+ cells don’t make CMs

23
Q

How does transplanting bone marrow cells help the myocardium after infarction?

A

It doesn’t really… clinical trials underway but show no new muscle but “no harm done”

**modest increase in heart function but transient

24
Q

How does transplanting induced pluripotent stem cells (iPSCs) help the myocardium after infarction?

A

Not sure (no clinical trials)

**iPSCs definitely do make rhythmic beating CMs, but worried about tumor formation, CM immaturity, and ability to integrate with host myocardium