M2 L2 Flashcards
(116 cards)
1
Q
what are cardiomyocytes
A
muscle cells of the heart — they make up the myocardium, which is the thick muscular layer of the heart wall responsible for pumping blood.
2
Q
What happens with low cardiomyocyte proliferation
A
Poor Repair After Injury (e.g., heart attack)
Dead cardiomyocytes are not replaced with new ones.
* Instead, fibroblasts deposit scar tissue (ECM) → this tissue can’t contract, weakening the heart.
3
Q
What is cardiomyocyte proliferation
A
Cardiomyocytes (heart muscle cells) normally do not divide much after birth, so the adult heart has very low regenerative capacity. If there’s low or no proliferation, the heart can’t replace lost or damaged cells well.
4
Q
What are the main energy sources for the fetal heart?
* describe mitochondria
A
Glucose and lactate circulating in the blood.
- low mitochondria, small, round
5
Q
What major metabolic change happens in the heart after birth?
A
The heart shifts from using carbohydrates to using fatty acids for energy.
6
Q
what is Cardiomyocyte Maturation
A
Cardiomyocyte maturation is the process by which heart muscle cells (called cardiomyocytes) develop from immature fetal cells into fully functional adult cells.
7
Q
what happens during cardiomyocyte maturation:
A
● Increased size
● Increased organization of contractile machinery, gap jxns, & organelles
● Increased ploidy (chromosome set)
8
Q
What dietary change occurs in the neonatal phase that affects heart metabolism?
A
Move from using glycolysis (yielding 2 ATP) to fatty acid oxidation (much more ATP)
this supports contractile and mitochondrial function
9
Q
What happens to the mitochondrial permeability transition pore (MTP) during healthy cardiac maturation?
How does the MTP behave in heart failure?
A
It shifts from being constantly open to a closed state, maintaining mitochondrial membrane potential.
In heart failure, there is an increased opening of the MTP.
10
Q
What is the contraction of the heart controlled by? What are those things activated by
A
controlled by waves of action
potentials (APs), which are initiated by cell membrane depolarization
11
Q
What is autorhythmicity and what are two ways it can occur?
A
The heart’s ability to produce its own rhythm (or heartbeat) without CNS input.
1) Pacemaker cells
2) Cardiomyocytes
12
Q
How do pacemaker cells work
A
initiate and conduct APs in the cardiac conduction system. They’re in the SA node and generate APs by themselves.
13
Q
How do cardiomyocytes work?
A
cannot initiate contraction on their own. They
undergo membrane depolarization upon receiving an AP and spread
that AP to neighboring cardiomyocytes through intercalated disks
14
Q
Where is the SA node?
A
Near the right
atrium and SVC
Starting pacemake
15
Q
Where is the AV node
A
Bottom of the right atrium, top of IVS
- Relays and slows current before reaching ventricles
16
Q
Where is the bundle of his
A
Cells originate from the AV
Node and enter the IVS
17
Q
Where are the purkinje fibers
A
Terminal nerve
fibers from the
Bundle of His and
found in the
ventricular
myocardium
18
Q
How do pacemaker cells fire an AP?
A
Pacemaker cells do not exhibit a resting membrane
potential. They “drift” towards depolarization until a
threshold is hit (green line) and an AP is fired.
19
Q
What do funny channels do (If)
A
During hyperpolarization (most negative voltage), funny channels (If) open.
These allow Na⁺ to flow in, slowly starting depolarization
20
Q
Pacemaker Activity of Autorhythmic cells
Explain whats happening in step 1
A
1) Increased inward Na+
current through voltage-gated
funny channels (If, which open
during hyperpolarization)
The incoming Na+ slowly starts depolarization.
21
Q
Pacemaker Activity of Autorhythmic cells
Explain whats happening in step 2
A
As the Na⁺ flows in (inward current), K⁺ channels begin to close (outward current), so less positive charge is leaving.
This amplifies depolarization (voltage becomes more positive).
22
Q
Pacemaker Activity of Autorhythmic cells
Explain whats happening in step 3
A
As depolarization continues, transient-type Ca²⁺ channels open briefly.
This allows a small burst of Ca²⁺ to enter, pushing the membrane toward the depolarization threshold potential.
nward Na+ current stops due
to closing of Funny channels close at this stage.
23
Q
Pacemaker Activity of Autorhythmic cells
Explain whats happening in step 4
A
Once threshold is hit, long lasting-type Ca²⁺ channels open.
This causes a big influx of Ca²⁺, triggering the action potential (sharp rise in membrane potential on the graph).
24
Q
Pacemaker Activity of Autorhythmic cells
Explain whats happening in step 5
A
L-type Ca²⁺ channels close, and voltage-gated K⁺ channels open.
K⁺ flows out (efflux) , bringing the membrane potential back down (repolarization).
Once it’s sufficiently negative again (hyperpolarized), the cycle restarts by reopening the If (funny) channels.
25
Pacemaker Cell Channels:
Na+
* channel name
* stimulus to open
* characteristics
* funny channels (If)
* very negative Vm (voltage gated)
* responsible for autorhymicity
26
Pacemaker Cell Channels:
K+
* channel name
* stimulus to open
* characteristics
* voltage gated K+ channels
* triggered to open at threshold; open at peak; close once membrane is repolarized
* slow kinetics (delayed open time)
27
Pacemaker Cell Channels:
Ca2+
* two channel names
* stimulus to open
* characteristics
* t-type (transient) Ca2+ channel AND L-type Ca2+ channel
* at threshold / when the cell is depolarizing
* long open time; sustained Ca2+ influx
28
Why is the
presence of
nonconductive
fibrous tissue
important?
This fibrous tissue is located at the atrioventricular (AV) junction, and it prevents electrical impulses from directly passing from the atria to the ventricles.
Without it, impulses could spread chaotically, and the ventricles might contract too early or at the wrong time, messing up the coordinated heartbeat.
29
What do intercalated discs do?
they carry AP signals from one cell to another
30
what does a desmosome do
holds structures together
31
Cariomyocite Action Potential
Explain whats happening in step 1
The inside of the cell is more negative due to leaky K⁺ channels that allow potassium to exit the cell.
This creates a stable negative resting membrane potential.
32
Cariomyocite Action Potential
Explain whats happening in step 2
A stimulus causes voltage-gated Na⁺ channels to open.
Na⁺ rapidly enters the cell, making the inside more positive — this is fast depolarization.
33
Cariomyocite Action Potential
Explain whats happening in step 3
Sodium channels inactivate.
Some K⁺ channels open briefly, allowing K⁺ to leak out — causing a small drop in membrane potential (slight repolarization).
The Na+ current decreases
34
Cariomyocite Action Potential
Explain whats happening in step 4
L-type calcium channels activated slowly, allowing Ca²⁺ to enter the cell.
This balances K⁺ leakage (reduces outward K+), keeping the membrane potential relatively stable (the "plateau").
35
Cariomyocite Action Potential
Explain whats happening in step 5
Ca²⁺ channels are inactivated and voltage-gated K⁺ channels open, letting K⁺ exit rapidly.
This returns the cell to -90 mV, the resting membrane potential.
36
Cardiomyocyte Cell Channels:
Na+
* channel name
* stimulus to open
* characteristics
* voltage-gated Na+ channel
* depolarization (specifically at threshold)
* automatically inactivate at peak
37
Cardiomyocyte Cell Channels:
Ca2+
* channel name
* stimulus to open
* characteristics
* L-type Ca2+ channel
* depolarization (voltage-gated) during refractory period
* depolarization (voltage-gated) during refractory period
38
Cardiomyocyte Cell Channels:
K+ --> LEAKY K+ CHANNEL
* stimulus to open
* characteristics
* negative Vm (closed during positive Vm)
* Closes during plateau phase
39
Cardiomyocyte Cell Channels:
K+ --> TRANSIENT K+ CHANNEL
* stimulus to open
* characteristics
* Positive Vm
* brief open time; closes shortly after opening
40
Cardiomyocyte Cell Channels:
K+ --> VOLTAGE GATED K+ CHANNEL
* stimulus to open
* characteristics
* depolarization; will close when the cardiac muscle cells are repolarized
* slow kinetics (delayed open time)
41
what is excitation-contraction coupling in a cardiomyocyte
how an electrical signal (the action potential) triggers contraction via calcium handling.
42
What triggers calcium entry in cardiomyocytes?
The action potential (AP) travels down the T-tubules and depolarizes the membrane, opening L-type calcium channels (LTCC), allowing Ca²⁺ to enter the cell.
43
What is calcium-induced calcium release (CICR)?
A small amount of Ca²⁺ entering through LTCC activates ryanodine receptors (RyR) on the sarcoplasmic reticulum (SR), releasing a larger amount of Ca²⁺ into the cytosol.
44
How does calcium trigger contraction?
The cytosolic Ca²⁺ binds to troponin on the sarcomere, which allows actin and myosin filaments to interact, causing muscle contraction.
45
What mechanisms remove calcium from the cytosol to allow relaxation?
SERCA pumps Ca²⁺ back into the SR, while the sodium-calcium exchanger (NCX) and Na⁺/K⁺ ATPase help expel Ca²⁺ from the cell.
46
Coordination of Cardiac Excitation with Pumping:
What does the electrical excitation begin with?
STEP 1: The SA node initiates an action potential.
Atrial filling (from vena cava)
Ventricular filling (passive flowing from AV valve)
47
Coordination of Cardiac Excitation with Pumping:
How/where does the action potential spread through the atria? (through which pathway?)
It spreads from the right atrium to the left via the interatrial pathway, and to the AV node via the internodal pathway (Step 2).
atrial filling
ventricular filling
48
Coordination of Cardiac Excitation with Pumping:
Why is there a delay at the AV node?
The 100-ms delay allows time for atria to contract and complete ventricular filling (Step 3).
atrial contraction
final ventricular filling
49
Coordination of Cardiac Excitation with Pumping:
After the AV node, where does the action potential go?
It travels down the interventricular septum via the Bundle of His and to the Purkinje fibers (Step 4).
final ventricular filling
50
Coordination of Cardiac Excitation with Pumping:
What do the Purkinje fibers do?
They distribute the action potential through the ventricular myocardium, causing ventricular contraction (Step 5).
51
What is ventricular and atrial diastole?
ventricles and atria relax and fill with blood
52
What is ventricular and atrial systole?
Ventricular Systole = ventricles contract and pump blood
Atrial Systole = atria contract to complete ventricular filling
53
whats an electrocardiogram
A measure of the heart’s electrical currents
* taken on body surface
54
How do cardiomyocyte cells and pacemaker cells work together?
Pacemaker cells initiate the electrical impulses that spread throughout the heart, triggering cardiomyocytes to contract.
The pacemaker cells’ ability to slowly reach the threshold and generate action potentials creates the heart’s rhythm, while cardiomyocytes respond by contracting to pump blood.
55
What initiates the heart’s electrical signal? Is it visible on the P wave?
SA node firing (not visible on ECG)
Step 1
56
What does the P wave represent on an ECG?
Atrial depolarization (atria contract)
Step 2
57
What does the PR segment represent?
Deplarizayion and delay at the AV node (lets atria finish contracting)
On ECG: Step 3, internodal delay
Step 3
58
Why isn’t atrial repolarization visible on the ECG?
It’s hidden behind the large QRS complex
step 4
59
What does the Q wave represent?
What does it look like
Early depolarization of the interventricular septum
* causes a slight downward slope as the signal is being direct away from the + electrode
60
What does the R wave represent?
what does the deflection look like
Main depolarization of the ventricles (massive contraction)
Positive deflection as
depolarization runs through the central portion of the ventricles
61
What does the S wave represent?
what does the deflection look like
Final depolarization spreading upward through the ventricles
Slight deflection due to the
depolarization traveling to the
top of the ventricles and away
from the + electrode (Lead II)
62
What happens during the ST segment?
ventricles are fully depolarized but not yet repolarizing (electrically quiet)
63
What does the T wave represent?
Ventricular repolarization (ventricles relax)
return to negative resting potential
64
What does the QRS complex as a whole represent?
Full ventricular depolarization (ventricles contract)
65
What are the limb leads?
The six limb leads are I, II, III, aVL, aVR, and aVF .
66
what is the leftmost side of the heart called?
the lateral wall
67
What does lead I measure?
electrical differences
between the right arm and left arm
68
What does lead II measure?
measures from the right arm to the left leg
69
What does lead III measure?
measures from the left arm to the left leg
70
What does it mean that leads leads aVF , aVL, and aVR are unipolar
measures the electrical potential at a single point (electrode) in relation to a reference point. This reference is a virtual electrode created by averaging the electrical activity from other leads or parts of the body.
rather than comparing like left arm and leg etc
71
Where is the aVF electrode placed?
* what is it useful to asses?
on the left leg. This lead is looking at the heart from the bottom (inferior) aspect, specifically toward the feet.
helps to assess the inferior surface of the heart. It is useful for detecting issues like inferior myocardial infarctions (heart attacks) that affect the bottom part of the heart.
72
Where is the aVL electrode placed?
on the left arm
This lead is looking at the heart from the left side, toward the left shoulder.
assesses the lateral surface of the heart (lateral wall). This lead is important for detecting lateral wall ischemia or infarction.
73
Where is the aVR electrode placed?
* what show?
on the right arm. This lead looks at the heart from the right shoulder.
aVR often shows what's happening on the right upper side of the heart. If it shows ST elevation, it may indicate a left main coronary artery occlusion or severe triple-vessel disease.
74
Depolarization of the heart goes from right to left; atria down to ventricles. Which Lead would be the most accurate representation of this?
Lead II because it runs from the right arm (-) to the left leg (+).
This vector aligns closely with the overall direction of cardiac depolarization:
* Right to left
* Superior to inferior (from atria to ventricles).
75
What do leads II, III, and aVF represent in an ECG?
* what useful to detect?
They represent the inferior surface of the heart (apex).
Useful for detecting inferior myocardial infarctions.
76
What do leads I, aVL, V5, and V6 represent in an ECG?
* what useful for
These are the lateral surface (LV wall)
most useful for detecting lateral wall infarcts
77
What do leads V1 and V2 represent in an ECG?
* damage usually caused by what?
They represent the interventricular septum, which separates the right and left ventricles.
Damage here is often caused by left anterior descending (LAD) artery blockage.
78
What do leads V3 and V4 represent in an ECG?
They represent the anterior surface of the heart (left ventricle), commonly affected in anterior myocardial infarctions due to LAD blockage.
79
Why is the QRS complex inverted in lead aVR?
the primary vector of ventricular depolarization, which is the electrical signal that causes the ventricles to contract, is directed away from the aVR lead. Since the electrical impulse is traveling away from aVR, the ECG shows a negative (inverted) deflection.
80
Why is lead II used for bedside monitoring?
Lead II gives a clear view of the heart’s electrical activity, especially the P wave, because it lines up well with the way signals normally travel through the heart. That makes it great for watching heart rhythm.
81
How does ECG wave deflection direction work?
* Toward the positive electrode → Positive (upward) deflection
* Away from the positive electrode → Negative (downward) deflection
negative usually arm pos is leg
82
This ECG representation is indicative of what
abnormality in heart rhythm?
Ventricular Fibrilation
83
What is Ventricular Fibrillation?
No discernable QRS complex
* Accompanied by irregular heart rhythm
84
This ECG representation is indicative or what
cardiomyopathy?
The arrow in the depicts
what specific feature in the ECG recording?
Myocardial infarction
ST segment elevation
85
What is an arrythmia
Alterations in rhythm or sequence of excitation
86
What is premature ventricular contraction?
* cause?
* trigger?
when the QRS complex occurs early
* due to damaged areas in the ventricular muscle or Purkinje fibers
* Stress, caffeine, alcohol, some medications.
87
What is ventricular fibrillation?
chaotic electrical activity in the ventricles with no discernible QRS complex
88
What is atrial fibrillation?
* cause?
No discernable P waves before QRS.
* : Erratic depolarization (signaling) from the atria overwhelming the AV node.
89
What is a complete heart block?
No communication between the atria and ventricle
* Atria continue to fire (P waves present).
* Ventricles beat on their own slower rhythm (QRS complexes present but unrelated to P waves).
90
What is an MI caused by
caused by an
atherosclerotic plaque
rupture or blockage due to
Coronary Artery Disease
(CAD)
91
what is ischemic heart failure
* cause
a type of heart failure that happens because part of the heart muscle is not getting enough oxygen-rich blood
* Adverse left ventricular (LV)
remodeling after MI due to changes in LV size, shape, function, cellular and molecular composition
92
In Lead II ECG readings, identify the specific pathology and describe one identifying feature.
Pathology: Atrial Fibrilation
Identifying feature: Irregularly irregular rhythm with absent P waves.
In Lead II, instead of distinct P waves before each QRS complex, you'll often see erratic baseline fibrillatory waves. The spacing between QRS complexes is irregular with no repeating pattern.
93
Between the pathology presented in A versus B. Which one would you expect to see a decrease in stroke volume?
A
ECG A
This shows ventricular fibrillation (VFib). This rhythm leads to no effective ventricular contraction.
ECG B
This shows premature ventricular contraction
(trigeminy), sporadic QRS complex.
94
A common anti-arrhythmic drug is a blocker of potassium channels in cardiomyocytes, preventing depolarization. How would this alter the cardiomyocyte action potential?
If k+ cant leave the cell, the membrane doesn't go back to its resting levels.
This means we are prolonging
the action potential and preventing hyperpolarization.
This makes the cells less excitatory (longer time before a refractory period)
95
What is a potential molecule/drug/factor that may antagonize the effects of potassium channel blockers?
Norepinephrine/epinephrine
96
Describe the main cellular responses following an acute myocardial infarction.
What happens with the cardiomyocytes, fibroblasts, and immune cells?
*inflammatory phase
* proliferative phase
* mature phase
During the inflammatory phase, the heart muscle cells
(cardiomyocytes) die, and immune cells move into the
damaged area.
In the proliferative phase, fibroblasts and cardiac myofibroblasts (cells that produce extracellular
matrix) migrate to the injury site while inflammation is
mostly resolved.
Finally, in the mature phase, cardiac fibroblasts are primarily myofibroblasts, and the scar
becomes stiff.
97
Name two clinical tests to determine if someone has just had an MI.
ECG for ST-elevation and Troponin testing of the serum.
98
what do Cardiac Fibroblasts do
Maintain the extracellular matrix (ECM), which provides structural support to heart tissue.
99
what do Cardiac Myofibroblasts do
These are activated versions of fibroblasts that appear primarily after cardiac injury, like a heart attack.
Secrete more ECM proteins (like collagen), which can lead to fibrosis—a stiffening or scarring of heart tissue.
100
What does the sympathetic innervate
the ventricles
101
What does the parasympathetic innervate
Innervation of atria, sinoatrial
node, and atrioventricular
node by the vagus nerve
(10th cranial nerve)
102
sympathetic NS effect on cAMP
* Increases cAMP activity (second messenger), which increases the
ability of pacemaker cells to depolarize and create APs
103
parasympathetic NS effect on cAMP
Decreases cAMP activity, keeping pacemaker cells more hyperpolarized,
prolonging the timing of new APs
104
How does the sympaethic NS affect pacemaker cells? (specific)
Promotes Na+ and Ca2+ inward movement (Funny;
Transient and Long-lasting Channels)
105
How does the sympaethic NS affect Atrial/Ventricular cardiomyocytes?
Increases contraction speed and strength (due to
increased Ca2+ in the cytosol)
* Increases relaxation speed (via the SERCA pump)
106
How does the sympathetic NS affect the adrenal medulla?
Reinforces sympathetic nervous system actions on
the cardiovascular system via the release of
catecholamines such as NE/E (long-lasting)
107
How does the parasymparthic NS affect pacemaker cells?
ACh increases K+ permeability, preserving hyperpolarization, making it harder to reach the depolarization threshold
* Limits Ca2+ and Na+ inward movement
108
How does the parasymparthic NS affect Atrial cardiomyocytes cells?
Reduces the slow inward current of Ca2+ during the
plateau phase
109
What are the 4 steps happening here?
1. NE/E binds to beta-adrenergic receptors & activates GPCRs
2. AC converts ATP → cAMP
3. cAMP activates HCN channels & PKA
4. PKA phosphorylates targets three things
110
What does the activation of HCN do?
The opening of HCN channels increases Na+ entry --> reducing time to depolarization
111
3 PKA phosphorylation targets in the sympathetic activation of cardiomyocytes:
What does the removal of PLB do?
PLB normally inhibits SERCA (sarcoplasmic reticulum Ca²⁺ pump).
removing it increases Ca²⁺ reuptake into the sarcoplasmic reticulum → helps with relaxation and readiness for next contraction.
112
3 PKA phosphorylation targets in the sympathetic activation of cardiomyocytes:
Effect of Activation of LTCC and RyR?
allow Ca²⁺ influx and release from SR respectively --> Ca2+ inc in cell
113
3 PKA phosphorylation targets in the sympathetic activation of cardiomyocytes:
effect of activation of sarcomeric proteins (TnI, cMyBP-C)?
Phosphorylation enhances contractility of the heart muscle → stronger contraction.
114
Why is long term elevation of cAMP harmful?
It increases the metabolic demand on heart cells (cardiomyocytes). Over time, this stress can cause cell death and hypertrophy (enlargement of heart muscle).
Result: worsened cardiac function and lower cardiac output.
115
Does atropine target the sympathetic or parasympathetic nervous system?
🔹Targets: Parasympathetic nervous system
🔹 Effect: Blocks it → allows sympathetic effects to take over
🔹 Use: Often to treat slow heart rate (bradycardia)
116
Why does limiting the activation of the parasympathetic
nervous system lead to reduced regeneration?
Limiting the parasympathetic nervous system:
Increases inflammation
Decreases growth factor signaling
Reduces stem cell activation
Lowers blood flow and nutrients
Prioritizes stress survival over tissue repair
➡️ All of which lead to reduced regeneration across various tissues.
