1 Cardiac Cell Biology Flashcards
What similarities do cardiomyocytes have with skeletal?
- basal lamina
- striated
- similar contractile proteins and mechanisms of contraction
How are cardiomyocytes different than skeletal?
- 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
What are two markers seen in the blood after and MI?
MB-creatine kinase and cTnl (cardiac troponin I) due to cardiomyocyte breakdown
Describe a cardiomyote (identify EM structures on photo)
What is the ratio of thick:thin filaments in a cardiomyocyte?
6 thin per thick filament (like skeletal!)
What is the function of intercalated discs?
They are sarcolemmal specializations that mediate cell-cell binding and enable cardiomyocytes to work as a single unit (producing rhythmic hearbeat)
Describe the layout of intercalated discs
- “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
Describe the excitation phase of cardiac contraction
**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
Describe cardiac muscle contraction
**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 does beta adrenergic stimulation affect the heart?
**Beta adrenergic receptors modulate the contractile response
cAMP increases -> protein kinases activated -> phosphorylation of L-type Ca channels and phospholamban
What are the effects of phosphorylation of L-type Ca channels and phospholamban?
- 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
What are the sympathetic and parasympathetic innervations of the myocardium?
- 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 are atrial cardiomyocytes different than ventricular?
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 are bundle of His cardiomyocytes different than ventricular?
Bundle of His CMs= “purkinje” CMs
- specialized for conduction
- endothelin -> cardiac myocyte -> purkinje fiber
What is the most abundant cell type in the heart?
“Cardiac” fibroblasts
**but myocytes are much larger and occupy most of the heart’s volume
Describe the timeline of a heart attack and the modifications afterwards
- 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
Can heart muscle regenerate?
“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)
Can skeletal myoblasts re-muscularize the injured heart?
Myoblasts= skeletal stem cells= satellite cells
**transplanted satellite cells cause arrhythmia and are therefore not therapeutically useful in the heart
Are cardiac fibroblasts CM stem cells?
NO; fibroblasts respond to injury by making a scar which is permanent and cannot contract (bad!)
Can pre-existing CMs proliferate to fix the heart?
Maybe… adult CM proliferation can be induced by inhibition of tumor suppressors and/or administration of pro-proliferative agents (e.g. Neuregulin)
Can endogenous adult stem cells re-muscularize the damaged heart?
Apparently not… their existence is controversial
What are c-kit+ cells?
Adult stem cells; autologous transplantation clinical trials underway to help myocardial repair after MI (results= “no harm done”)
**cKit+ cells don’t make CMs
How does transplanting bone marrow cells help the myocardium after infarction?
It doesn’t really… clinical trials underway but show no new muscle but “no harm done”
**modest increase in heart function but transient
How does transplanting induced pluripotent stem cells (iPSCs) help the myocardium after infarction?
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
