Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Cardiovascular Unit > Cardiac Cell Biology > Flashcards

Cardiac Cell Biology Flashcards

1
Q

cardiac cell biology compared with skeletal muscle

A 
similarities:
• basal lamina
• striated
• contractile proteins similar (but not identical)
• mechanism of contraction is similar
differences:
• involuntary (vs. voluntary skeletal muscle, which is operated by motor nerves)
• myocytes are smaller 
• 1-2 central nuclei (sometimes 3) (vs. skeletal muscles, which can have 100s of nuclei)
• myocytes branch
• ++++ vascular
• ++++ mitochondria
• ++++ myoglobin
• ++++ lipid droplets
• MB-creatine kinase
• intercalated discs (nothing like this in skeletal muscle)
=>cardiac muscle is aerobic!!
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

cardiac myocytes–when seen on LM longitudinal section

A
  • cardiac myocytes branch (arrowheads)
  • intercalated discs (arrows) are at boundaries between myocytes • cross-striations are faint, in contrast w skeletal muscle
  • nuclei are central
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

cardiac myocytes–when seen on LM cross section

A

• myofibrils are discernable
• venule (V) & capillaries(C) = highly vascular
- (note RBCs in capillaries)
-no striations seen in cross section

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

cardiac myocyte–when seen on EMs

A 
• sarcomeres (fundamental unit of cardiac muscle contraction) aligned as in skeletal muscle
• many more mito!!!
• lots of glycogen
Note:
• central nucleus
• endothelial cell (making a capillary)
• profuse mitochondria
-MB-CK seen
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

cardiac myocyte–when seen on EM in cross section

A

Note:
• basal lamina (BL) v. adjacent cardiac myocytes
• 6 thin filaments per thick filament
• SR surrounds myofibrils

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

intercalated discs (IDs)

A
  • sacrolemma specializations v. adjoining cells

- enable cardiac myocytes to work as a unit, as if they were in a syncytium!!

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

intercalated discs (IDs)–cross adjacent myocytes in “staircase fashion”

A
  • transverse: transmits force; modified Z-band
    • fascia adherens (N-cadherins) and desmosomes
  • lateral: cell-cell signaling
    • gap junctions (nexus) and some desmosomes
    • Note: some textbooks don’t consider the lateral component as a part of the intercalated disc.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

intercalated disc ultrastructure

A

-‘last’ I-band(s) attaching to “Z-line
-gap junctions are along this lateral border
-N-cadherin in intercellular space
• Discs cross adjacent cells in stepwise fashion.
• fascia adherens ~ zonula adherens (but doesn’t encircle the cell)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Excitation-Contraction Coupling

A

Excitation (electrical)
• Action Potential: depolarization –> T-tubules
• Phase 2 of AP: L-type Cav1.2–>Ca++ influx
• Ryanodine Receptors in SR:–>–>–>Ca++ (CICR=Calcuim Induced Calcium Response) (a lot more influx of Ca++ is generated from this)

Contraction (physical response to the electrical change)
• Ca++ binds troponin-C  tropomyosin moves
• myosin head is activated by ATP hydrolysis & myosin head binds actin
• power stroke = contraction: myosin pulls actin into the A-band & the sarcomere shortens

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

when thin filaments move, sarcomeres shorten. what happens during contraction and relaxation??

A

During Contraction
• A-band length stays same
• I-band length shortens Relaxation

  • L-type channels inactivate
  • Ca++ is re-sequestered into SR via SERCA (sarco-endoplasmic reticulum Ca++ ATPase)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

effect of B-adrenergic stimulation (catecholamines-i.e. norepinephrine)

A

increased cAMP levels–>activated protein kinases–>phosphorylation–>L-type Ca++ flux–>enhanced contractile force

increased cAMP levels–>activated protein kinases–>phosphorylation–>phospholamban (in SR)–>increased Ca++ uptake by SR–>relaxation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

cardiac myocyte innervation

A

the myocardium has an intrinsic, rhythmic beat

vagus nerve (parasympathetic)–>ACh–>muscarinic receptors–>regulate HR (relaxation)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

regional histologic differences in the heart: atria, SA, AV nodes

A

•atria, SA, AV nodes: smaller myocytes with fewer striations
– in atria, membrane-bound granules (G) contain atrial natriuretic factor (ANF aka ANP).
– ANF (ANP) has many functions, including vasodilation.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

regional histologic differences in the heart: ‘Bundle of His’

A

• ‘Bundle of His’ contains ‘Purkinje’ myocytes – 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

regional histologic differences in the heart: endocardium

A

• endocardium: single layer of endothelial cells

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

regional histologic differences in the heart: “cardiac” fibroblasts

A

• “cardiac” fibroblasts: the heart’s most abundant cell type - but, myocytes are larger & comprise most of the heart volume

17
Q

chronology of a heart attack

A
  1. immediate: myocyte death–> MB-CK & cTnI
  2. +15 hrs: inflammation
  3. +2-3 days: wound healing via cardiac fibroblasts (collagen deposition; fibrosis to heal wound=good, BUT collagen does not contract like cardiofibers can and should contract)
  4. +2-4 days: angiogenesis (clinical enhancement via VEGF, FGF?)
  5. scar deposition (due to collagen cross-linking
18
Q

during a heart attack, cardiomyocytes die. Inability to regenerate cardiac muscle=major clinical problem. can heart muscle regenerate?

A
  • Dogma pre-2000: No. We received our allocation of cardiac myocytes a long time ago.
  • 2000-2010: The myocardium naturally regenerates, but at a rate that is too low to restore effective function.
19
Q

Can skeletal myoblasts – i.e. skeletal muscle stem cells – re-muscularize the injured heart?

A

This approach has been abandoned due to inefficacy and arrhythmia.

  • ~3% of nuclei in skeletal muscle are skeletal myoblasts–>can regenerate skeletal muscle
  • saw some improvement in function, but arrhythmias arose! makes sense…skeletal muscles do not contract in the same way as cardiac muscle
20
Q

Are “cardiac” fibroblasts (CFs) endogenous CM stem

cells?

A

• No. Fibroblasts cannot become myocytes.
• At least 1 CF borders each CM.
• But, fibroblasts can’t regenerate the heart.
• Fibroblasts respond to injury by making a scar.
• Scars are permanent.
• Scars don’t contract.
• This is not good.
But, as of 2012, CFs may be “induced” into CMS!

21
Q

Can existing myocytes mobilize to fix damaged myocardium?

A

– Maybe
–Adult cardiomyocyte proliferation can be induced by…
• …inhibiting p38 MAP kinase
• …pro-proliferative agents
• Phase 1 trials (safety & efficacy) are planned to evaluate neuregulin.
• Alternatively, can tumor suppressors (such as Rb, p16ink) in cardiomyocytes be inhibited to permit cell replication?

22
Q

Can adult stem cells in the heart fix damaged heart?

A

– Obviously not; but, maybe they could be mobilized to do so.
– These adult stem cells are identified per expression of a stem cell marker termed c-Kit.
– Their existence is controversial; however, adult cardiac stem cells likely exist, in ‘niches’.
– Can they be mobilized?
– How to mobilize them?
• Treat heart with drugs and/or growth factors to mobilize & expand these stem cells in their niches.

23
Q

Can c-Kit+ adult stem cells be transplanted to fix injured myocardium?

A

Perhaps, as per an ongoing Phase 1 clinical trial,
a. Isolate c-Kit+ cells from R. atrial appendage or R. IV. septum via catheter.
b. Expand c-Kit+ cells in culture.
c. Transplant 2 million c-Kit+ cells back into same patient (so no immune rejection).
d. Some function is restored & infarcted area is reduced, while “No harm is done”.
• These positive effects are likely mediated via ‘paracrine’ factors that enhance the heart. (Studies in animals have shown that c- Kit+ cells don’t make muscle.)

24
Q

Do transplanted bone marrow cells fix injured myocardium?

A

• Idea: Bone marrow cells might migrate to the heart & take up residence as adult stem cells. Evidence:
– Transplant female heart into male host.
– ‘Male’ cells invade this female heart.

25
Q

Can transplanted bone marrow cells fix the heart?

A

• Maybe.
• Harvest bone marrow cells from patient. – from bone marrow or from peripheral blood
• Transplant into same patient via catheter.
• Animal studies revealed little or no re-muscularization. – But, functional benefit occurred (via ‘paracrine’ effect?).
• Phase 1 clinical trials have been performed – ‘No harm is done.’
– Result: Modest increase in heart function, albeit transient
– Current Focus: identify the best bone marrow cell type.
• Example: mesenchymal stem cells (MSCs)

26
Q

Transplantation of CMs derived from induced pluripotent cells (iPSCs)?

A

• iPSCs–>200 different cell types
• Generated via “reversal of aging”
– patient’sdermalfibroblasts/Tcells+3-4 transcription factors–> iPSCs + cardiomyogenic growth factors –> cardiomyocytes –> transplant into same patient
–>after the last two years, we know this is a definite possibility!
-Beating cardiomyocytes can definitely be generated from iPSCs, whereas it remains uncertain whether contractile cells can be generated from adult stem cells.
-However, inefficiency & potential tumorigenesis are still formidable problems.

Cardiovascular Unit (16 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions