Name some similarities and differences between skeletal and cardiac muscles
- Basal lamina
- 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)
To satisfy high energy demand, cardiac myocytes contain an abundance of what?
mitochondria and glycogen
Name the two parts of the intercalated discs
Describe the transverse part of the intercalated discs
Transmits contractile force. Consists of:
- fascia adherens (partially encircles the cell)
Describe the lateral part of the intercalated discs
Transmits cell-to-cell signals (function to maintain rhymicity of the heartbeat) via:
- nexuses (gap junctions, connexons -> 6 connexin proteins)
Cardiac myocytes contain thin and thick filaments in approximately what ratio?
During contraction, which band remains the same length? Shortens?
the A-band stays the same length
The I-band shortens
Name the protein responsible for calcium sequestration during cardiac myocyte relaxation
(sarco-endoplasmic reticulum Ca++ ATPase)
Describe the process of beta-andrenergic stimulation (i.e. norepinephrine)
- increased cAMP levels
- activated protein kinases
- phosphorylation of L-type Ca++ channel activation
- increase Ca++ flux
- enhanced contractile force
- phosphorylation of phospholambin in the SR
- increased Ca++ uptake by the SR
Innervation of the heart regulates what aspect of the heartbeat?
via the vagus nerve (PNS) and autonomic nerves (SNS)
Name some unique characteristics of cardiac myocytes found in the atria, SA, and AV nodes
- smaller myocytes with fewer striations
- antrial natriuretic peptide (ANP) contained in granules
What is the function of atrial natriuretic peptide (ANP)?
Many functions, most notably vasodilation and stimulation of the kidney to eliminate water and sodium
What triggers the development of Purkinje fibers (myocytes)?
endothelin screted by neighboring endothelial cells
Describe the endocardium
single-layer cellular lining the lumen of the ventricles, continuous with the endothelial lining of the rest of the vascular system
What is the most abundant cell type (by number) in the heart? By volume?
number: cardiac fibroblasts
volume: cardiac myocytes
MB-CK and cTnl are markers for what?
Myocardial infarction (MI)
Describe the chronology of a heart attack (MI):
- Immediate: myocyte death, resulting in increased MB-CK and cTnl
- ~15h: inflammation
- ~2-3d: wound healing via cardiac fibroblasts (scarring via collagen deposition)
- ~2-4d: angiogenesis
- Scar deposition (collagen cross-linking)
Can heart muscle regenerate?
Likely, albeit at a rate too slow for effective regeneration
Increased serum levels of MM-CK are an indicator for what?
MM-CK (skeletal myocyes creatine kinase) - indicates muscular dystrophy
Are transplanted skeletal myoblasts a desirable method for replacing/regenerating cardiac myocytes? Why?
No. This method has largely been abandoned due to inefficacy and significant risk of cardiac arrhythmia
What is the main issue with using cardiac fibroblasts as a possible replacement therapy?
Inefficiency. So far, only about 0.1% of re-differentiated cells contain sarcomeres and sponaneously contract
Name (5) proposed methods of mobilizing or transplanting cells to heal/replace damaged heart tissue:
- Mobilization of existing healthy CMs (endogenous), including via p38 MAP kinase pathway or inhibition of tumor suppressor genes
- Mobilization of adult heart stem cells from 'niches', targeting c-KIT (CD117)
- Transplanation of adult heart stem cells, including harvesting c-KIT positive cells, expanding, then re-implanting
- 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).
- Transplantation of cardiomyocytes derived from pluripotent stem cells (induced pluripotent stem cells a.k.a. iPSCs).
What is one of the biggest challenges in developing iPSC therapy?
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
What is the marker used to identify adult cardiac stem cells (provided the actually exist)?