Chapter 46 Flashcards
1
Q
A
2
Q
What percentage of total ventricular volume and weight do cardiomyocytes account for?
A
75%
3
Q
What is the structure of a ventricular myocyte?
A
- Brick shaped
- 150 × 20 × 12 μm
- Binucleate, some with 3-4 nuclei
- Connected at long ends by specialized junctions
- Have branched cross striations
4
Q
Define myofiber.
A
Group of cardiomyocytes held together by surrounding collagen connective tissue
5
Q
What is the role of the sarcoplasmic reticulum (SR)?
A
Critical for calcium (Ca2+) cycling
6
Q
What are the parts of the sarcoplasmic reticulum?
A
- Ryanodine receptors (RyRs)
- Longitudinal, free or network SR
- SERCA (sarcoendoplasmic reticulum Ca2+–adenosine triphosphatase)
7
Q
What is the function of SERCA?
A
ATP-consuming Ca2+ uptake pump that transports Ca2+ back into the SR from the sarcoplasm
8
Q
What is the function of jSR-T-tubule junctions?
A
Produce synchronous Ca2+ transients that control contraction
9
Q
What is the role of caveolae in cardiac muscle cells?
A
Key localized signaling cascade
10
Q
What happens during chronic high Ca2+ levels?
A
- Mitochondrial Ca2+ uptake occurs at the expense of ATP production
- Leads to cell death
11
Q
What initiates the contraction cycle?
A
Ca2+ binding to troponin C
12
Q
What is the function of titin?
A
Connects thick filament to the Z-line and stabilizes sarcomeric structure
13
Q
What does the Frank-Starling effect describe?
A
The relationship between sarcomere length and strength of contraction
14
Q
What is the significance of calcium in muscle contraction?
A
Calcium binding to troponin C allows myosin binding to actin, enabling the cross-bridge cycle
15
Q
What is the role of myosin light chains?
A
- MLC-1: Essential myosin light chain
- MLC-2: Regulatory myosin light chain
16
Q
What are the two main myosin isoforms?
A
- Beta-myosin heavy chain (β-MHC)
- Alpha-myosin heavy chain (α-MHC)
17
Q
What is the function of omecamtiv mecarbil?
A
Activates myosin ATPase and enhances myosin cross-bridge formation
18
Q
What is the role of dystrophin in cardiac muscle?
A
Mediates force transmission between the intracellular cytoskeleton and the extracellular matrix
19
Q
What are the calcium channels mentioned?
A
- T-type Calcium channels
- L-type Calcium channels
20
Q
What is the difference between T-type and L-type calcium channels?
A
- T-type: Open at more negative voltage, short burst of opening
- L-type: Long-lasting, concentrated in T tubules
21
Q
What does the term ‘cross-bridge cycling’ refer to?
A
Interaction of myosin heads with actin filaments
22
Q
What occurs during isometric contraction?
A
Cross bridges rotate but cannot fully move the actin filament
23
Q
What happens during the power stroke?
A
Myosin head flexes and moves the actin filament by approximately 10 nm
24
Q
What is the effect of increased [Ca2+]i on the cross-bridge cycle?
A
Increases the saturation of Ca2+ binding sites on troponin C, enhancing cross-bridge formation
25
What is the role of scaffolding proteins?
Bring interacting molecules close together for signaling
26
What is the significance of the sarcomere length at the end of diastole?
Major influence on the strength of contraction
27
What is the significance of SR Ca2+ content in cardiac function?
Critical to normal cardiac function and electrophysiology; abnormalities contribute to systolic and diastolic dysfunction and arrhythmias
28
Where are RyR channels primarily located?
In the jSR membrane at the junctions with the T tubule
29
What is the function of RyR2 in cardiac myocytes?
Functions both as a Ca2+ channel and as a scaffolding protein that localizes key regulatory proteins to the jSR
30
What triggers the activation of jSR RyR channels?
Local cleft [Ca2+] increases sufficiently to activate at least one local jSR RyR
31
What causes the turning off of Ca2+ release from the SR?
When [Ca2+] SR drops by approximately 50%
32
What mediates calcium-dependent inactivation?
Binding of Ca2+ to Calmodulin (CaM)
33
What effect does high [Ca2+] SR have on RyR2?
Favors opening of RyR2 channels
34
What are calcium sparks?
Spontaneous local SR Ca2+ release events due to local Ca2+-induced Ca2+ release
35
What is the primary protein responsible for calcium uptake into the sarcoplasmic reticulum?
SERCA
36
What is the dominant form of SERCA in cardiomyocytes?
SERCA2a
37
What is the effect of phospholamban (PLB) on SERCA2a?
Reduces the affinity of SERCA for cytosolic Ca2+
38
What happens when PLB is phosphorylated?
Inhibitory effect on SERCA2a is relieved, increasing rates of SR Ca2+ uptake
39
What role does calsequestrin play in the sarcoplasmic reticulum?
Ca2+-storing protein that enhances local availability of Ca2+ for release
40
What is the main mechanism for extruding Na+ from cardiac myocytes?
Na+, K+-ATPase
41
What is the Bowditch phenomenon?
Force-frequency relationship where increasing HR increases Na+ and Ca2+ entry
42
What is the role of Ca2+/Calmodulin-Dependent Protein Kinase II (CaMKII)?
Alters gating of I Na, I Ca, and other channels
43
What are the two types of calcium channels mentioned?
T-type and L-type Ca2+ channels
44
Which ion exchanger is responsible for extruding most of the Ca2+ that entered by ICa?
Na+/Ca2+ exchange (NCX)
45
What is the main effect of digitalis glycosides on myocytes?
Increase in [Na+]i, limiting the ability of NCX to extrude Ca2+
46
What is the role of sodium channels during an action potential?
Carry the cardiac Na+ current and drive the upstroke of the AP
47
What is the significance of late sodium current (INaL)?
Creates a persistent influx of Na+ throughout the plateau of the AP
48
How does an increase in heart rate affect calcium levels in the SR?
Increases Ca2+ in the SR due to more frequent ICa pulses and less time for removal
49
What is the relationship between SERCA and NCX in heart failure?
SERCA is downregulated and NCX may be upregulated
50
What does the term 'electrogenic' refer to in the context of Na+, K+-ATPase?
It carries an outward current
51
What effect does phosphorylation have on phospholemman (PLM)?
Relieves the inhibitory effect on Na+, K+-ATPase
52
What can happen if digitalis glycosides are overdosed?
Can lead to myocyte Ca2+ overload and trigger arrhythmias
53
Name two signaling factors that potentiate norepinephrine release.
* Adenosine
* Nitric oxide (NO)
## Footnote
Angiotensin II also plays a role in this process.
54
What is the main positive inotropic response mediated by beta1 receptors?
Adrenergic activation
## Footnote
Beta1 receptors account for 80% of cardiac receptors.
55
Which adrenergic receptor subtype is primarily responsible for vasoconstriction?
Alpha1 receptors
## Footnote
They are found in the sarcolemma of vascular smooth muscle.
56
What is the role of G proteins in cellular signaling?
They carry the signal from the agonist and receptor to the enzyme system producing cAMP
## Footnote
The superfamily of G proteins binds guanine triphosphate (GTP).
57
What is the function of adenylyl cyclase?
Catalyzes the formation of cAMP
## Footnote
It is the only enzyme that produces cAMP using ATP as a substrate.
58
What does Protein Kinase A (PKA) do in cardiac cells?
Mediates key effects of cAMP by phosphorylating target proteins
## Footnote
PKA-II predominates in cardiac cells.
59
What are the five main determinants of ventricular mechanical performance?
* Preload
* Afterload
* Contractility
* Lusitropy
* Heart rate
## Footnote
These factors collectively influence cardiac output.
60
What is the Windkessel effect?
Aortic recoil that maintains blood flow from the LV to the aorta during reduced ejection
## Footnote
It helps stabilize blood flow during the cardiac cycle.
61
What is the difference between cardiologic systole and physiologic systole?
Cardiologic systole starts at isovolumic contraction or mitral valve closure (M1) to the closure of the aortic valve (A 2 ), longer than physiologic systole; physiologic systole is from isovolumic contraction to peak ejection
## Footnote
Cardiologic systole is longer than physiologic systole.
62
What is the primary physiological role of nitric oxide (NO) in the heart?
Acts as a unique messenger affecting various signaling pathways
## Footnote
It is produced by three isoenzymes in the heart.
63
What is Starling’s Law of the Heart?
The principle that the greater the heart volume, the greater the energy of contraction
## Footnote
It relates to the preload and cardiac output.
64
What does the term 'afterload' refer to?
Forces opposing left ventricular ejection
## Footnote
It is inversely proportional to stroke volume.
65
What is the effect of Ca2+/Calmodulin-Dependent Protein Kinase II (CaMKII) on cardiac function?
Regulates various cardiac functions and enhances L-type Ca2+ channel activity
## Footnote
It can also lead to arrhythmogenic consequences.
66
What is the role of neuregulins in cardiac signaling?
Maintain activity of the muscarinic receptor, balancing parasympathetic and beta-adrenergic stimulation
## Footnote
They are important for normal cardiac function.
67
Fill in the blank: The phase of _______ occurs when pressures in the atrium and ventricle equalize, and LV filling virtually stops.
[diastasis]
## Footnote
This phase is critical for understanding diastolic function.
68
What happens during atrial systole?
Contributes to renewed filling of the ventricle after diastasis
## Footnote
It is particularly important at high heart rates.
69
What is the relationship between wall stress during systole and stroke volume?
Inversely proportional
## Footnote
As wall stress increases, stroke volume tends to decrease, indicating a complex interaction in cardiac dynamics.
70
What does Starling’s Law of the Heart state?
LV volume = cardiac output
## Footnote
This law describes how the heart's output increases with increased volume of blood filling the heart.
71
How does venous filling pressure affect heart volume?
Larger volume increases contraction energy
## Footnote
The heart contracts more forcefully when it is filled with a greater volume of blood, within physiological limits.
72
What is the relationship between LVEDV and LVEDP?
Curvilinear
## Footnote
The slope of this relationship reflects LV compliance, indicating how easily the ventricle can fill with blood.
73
What are surrogate measures for LV volume?
LVEDP or pulmonary capillary wedge pressure
## Footnote
These measures are commonly used instead of directly measuring LV volume.
74
How can venous filling pressure be measured in humans?
By cardiac catheterization
## Footnote
This invasive procedure allows for direct measurement of pressures within the heart and great vessels.
75
What effect does diastolic stretch of the left ventricle have?
Increases force of contraction
## Footnote
This is due to the positive inotropic effect and increased lusitropic effect.
76
What is the Frank-Starling law?
Increased Volume -> increase Contraction
## Footnote
This principle describes how, within physiological limits, an increase in ventricular volume leads to a stronger contraction.
77
How can the increase in strength of contraction be categorized?
Frank-Starling effect or inotropic effect
## Footnote
The Frank-Starling effect relates to sarcomere length, while the inotropic effect involves changes in calcium dynamics.
78
What is the Anrep Effect?
Abrupt Increase in Afterload increases force and pressure at the next beat
## Footnote
This effect occurs due to a sudden rise in aortic pressure, which increases EDV and subsequently enhances the next contraction.
79
What happens during a slower adaptation in the Anrep Effect?
Inotropic state of the heart increases
## Footnote
This adaptation takes seconds to minutes and reflects a more gradual increase in contractile strength.
