Cardiac Cell Biology - Lough

Question 1

Name some similarities and differences between skeletal and cardiac muscles

Answer 1

Similarities:

• Basal lamina
• Striated
• Similar (not same) contractile proteins
• Similar (not same) mechanism of contraction

Differences (cardiac vs. skeletal):

• Involuntary (vs. voluntary)
• smaller myocytes (15um x 100um) - (vs. mm)
• 1-2 (sometimes 3) centrally located nuclei (vs. 100’s)
• branching mycytes (vs linear)
• more vascular
• many more mitochondria
• more myglobin
• more lipid droplets
• MB-CK (vs. MM-CK)
• Intercalated discs (no equivalent in skeletal myocytes)

Question 2

To satisfy high energy demand, cardiac myocytes contain an abundance of what?

Answer 2

mitochondria and glycogen

Question 3

Name the two parts of the intercalated discs

Answer 3

Transverse part

Lateral part

Question 4

Describe the transverse part of the intercalated discs

Answer 4

Transmits contractile force. Consists of:

• fascia adherens (partially encircles the cell)
• desmosomes
• N-cadherin

Question 5

Describe the lateral part of the intercalated discs

Answer 5

Transmits cell-to-cell signals (function to maintain rhymicity of the heartbeat) via:

• nexuses (gap junctions, connexons -> 6 connexin proteins)
• desmosomes

Question 6

Cardiac myocytes contain thin and thick filaments in approximately what ratio?

Answer 6

6:1 (thin:thick)

Question 7

During contraction, which band remains the same length? Shortens?

Answer 7

the A-band stays the same length

The I-band shortens

Question 8

Name the protein responsible for calcium sequestration during cardiac myocyte relaxation

Answer 8

SERCA

(sarco-endoplasmic reticulum Ca++ ATPase)

Question 9

Describe the process of beta-andrenergic stimulation (i.e. norepinephrine)

Answer 9

1. increased cAMP levels
2. activated protein kinases
3. phosphorylation

Branch 1:

1. phosphorylation of L-type Ca++ channel activation
2. increase Ca++ flux
3. enhanced contractile force

Branch 2:

1. phosphorylation of phospholambin in the SR
2. increased Ca++ uptake by the SR
3. relaxation

Question 10

Innervation of the heart regulates what aspect of the heartbeat?

Answer 10

Rate

via the vagus nerve (PNS) and autonomic nerves (SNS)

Question 11

Name some unique characteristics of cardiac myocytes found in the atria, SA, and AV nodes

Answer 11

• smaller myocytes with fewer striations
• antrial natriuretic peptide (ANP) contained in granules

Question 12

What is the function of atrial natriuretic peptide (ANP)?

Answer 12

Many functions, most notably vasodilation and stimulation of the kidney to eliminate water and sodium

Question 13

What triggers the development of Purkinje fibers (myocytes)?

Answer 13

endothelin screted by neighboring endothelial cells

Question 14

Describe the endocardium

Answer 14

single-layer cellular lining the lumen of the ventricles, continuous with the endothelial lining of the rest of the vascular system

Question 15

What is the most abundant cell type (by number) in the heart? By volume?

Answer 15

number: cardiac fibroblasts
volume: cardiac myocytes

Question 16

MB-CK and cTnl are markers for what?

Answer 16

Myocardial infarction (MI)

Question 17

Describe the chronology of a heart attack (MI):

Answer 17

1. Immediate: myocyte death, resulting in increased MB-CK and cTnl
2. ~15h: inflammation
3. ~2-3d: wound healing via cardiac fibroblasts (scarring via collagen deposition)
4. ~2-4d: angiogenesis
5. Scar deposition (collagen cross-linking)

Question 18

Can heart muscle regenerate?

Answer 18

Likely, albeit at a rate too slow for effective regeneration

Question 19

Increased serum levels of MM-CK are an indicator for what?

Answer 19

MM-CK (skeletal myocyes creatine kinase) - indicates muscular dystrophy

Question 20

Are transplanted skeletal myoblasts a desirable method for replacing/regenerating cardiac myocytes? Why?

Answer 20

No. This method has largely been abandoned due to inefficacy and significant risk of cardiac arrhythmia

Question 21

What is the main issue with using cardiac fibroblasts as a possible replacement therapy?

Answer 21

Inefficiency. So far, only about 0.1% of re-differentiated cells contain sarcomeres and sponaneously contract

Question 22

Name (5) proposed methods of mobilizing or transplanting cells to heal/replace damaged heart tissue:

Answer 22

1. Mobilization of existing healthy CMs (endogenous), including via p38 MAP kinase pathway or inhibition of tumor suppressor genes
2. Mobilization of adult heart stem cells from ‘niches’, targeting c-KIT (CD117)
3. Transplanation of adult heart stem cells, including harvesting c-KIT positive cells, expanding, then re-implanting
4. Transplanation of bone marrow cells, specifically MSCs (mesenchymal stem cells), which have been implicated in bone marrow-derived regeneration of heart muscle (male-female heart transplant example).
5. Transplantation of cardiomyocytes derived from pluripotent stem cells (induced pluripotent stem cells a.k.a. iPSCs).

Question 23

What is one of the biggest challenges in developing iPSC therapy?

Answer 23

Ensuring 100% efficient directed differentiation

Failure to differentiate all iPSCs to cardiac myocytes could result in the growth of unwanted cell types or even tumors

Question 24

What is the marker used to identify adult cardiac stem cells (provided the actually exist)?

Answer 24

c-kit