Cardiac Muscle Contraction Flashcards
Is the basic contractile machinery in cardiac and skeletal muscle similar?
Yes, their cell structure is basically the same
Describe the steps involved in excitation-coupling in cardiac muscle
1) The cardiac action potential is initiated in the myocardial cell membrane, and the depolarization spreads to the interior of the cell via the T tubules which results in an inward Ca2+ current
2) Entry of Ca2+ into the myocardial cell produces an increase in intracellular Ca2+ concentration which triggers the release of more Ca2+ from the endoplasmic reticulum
3) Ca2+ binds to troponin C, moving tropomyosin out of the way allowing actin and myosin to interact
4) Cross-bridges form and then break, resulting in the thin and thick filaments to move past each other to produce tension
When does relaxation occur?
When Ca2+ is reaccummulated in the sarcoplasmic reticulum by the action of Ca2+ ATPase
What is contractility, or iontropism?
The intrinsic ability of myocardial cells to develop force at a given muscle cell length
Agents that produce an increase in contractility are said to have _____ inotropic effects
positive
What do positive inotropic effects do?
They increase both the rate of tension development and the peak tension
Agents that produce an decrease in contractility are said to have _____ inotropic effects
negative
What do negative inotropic effects do?
They decrease both the rate of tension development and the peak tension
What is contractility directly related to?
intracellular calcium concentration
What are the 2 factors in which the amount of Ca2+ released from the sarcoplasmic reticulum depend on?
- size of the inward Ca2+ current during the plateau of the myocardial action potential
- the amount of Ca2+ previously stored in the sarcoplasmic reticulum for release
Stimulation of the sympathetic nervous system has a ____ inotropic effect
positive
What are the 3 important features of the positive inotropic effect of the sympathetic nervous system?
- increased peak tension
- increased rate of tension development
- faster rate of relaxation
Faster relaxation means that the contraction is _____.
shorter
What are the 2 proteins that are phosphorylated to produce an increase in contractility?
- sarcolemmal Ca2+ channels
- phospholamban
How does phosphorylation of the sarcolemmal Ca2+ channels produce an increase in contractility?
There is increased inward Ca2+ current during the plateau and increased trigger Ca2+, which increases the amount of Ca2+ released from the sarcoplasmic reticulum
What is phospholamban?
A protein that regulates Ca2+ ATPase in the sarcoplasmic reticulum
How does phosphorylation of phospholamban increase contractility?
It stimulates the Ca2+ ATPase, resulting in greater uptake and storage of Ca2+ by the sarcoplasmic reticulum
What are the 2 effects of increased Ca2+ uptake by the sarcoplasmic reticulum?
- it causes faster relaxation
- it increases the amount of stored Ca2+ for release on subsequent beats
Stimulation of the parasympathetic nervous system has a negative inotropic effect on what?
the atria
The G protein that is coupled to the muscarinic receptors of the parasympathetic nervous system causes a _____ in contractility. Explain why…
decrease
Because it is inhibitory
What are the 2 factors that are responsible for the decrease in atrial contractility caused by the parasympathetic nervous system?
- ACh decreases inward Ca2+ current during the plateau of the action potential
- ACh shortens the duration of action potential and, indirectly, decreases the inward Ca2+ current (by shortening the plateau phase)
What are cardiac glycosides?
a class of drugs that act as positive inotropic agents
What is the action of cardiac glycosides?
inhibition of Na+ - K+ ATPase
Inhibition of Na+ - K+ ATPase results in ____ inotropic effects
positive
Describe the mechanism of the positive inotropic effect of cardiac glycosides
1) cardiac glycosides inhibit Na+ - K+ ATPase at the extracellular K+ binding site
2) less Na+ is pumped out of the cell, increasing the intracellular Na+ concentration
3) a Ca2+ - Na+ exchanger pumps Ca2+ out of the cell against an electrochemical gradient in exchange for Na+ moving into the cell
4) less Ca2+ is pumped out of the cell and intracellular Ca2+ concentration increases
5) tension increases due to an increase in intracellular Ca2+ concentration
What are cardiac glycosides typically used for therapeutically?
in the treatment of congestive heart failure
What does the maximal tension that can be developed by a myocardial cell depend on?
its resting length
At what length do cardiac cells develop maximal tension?
2.2 micrometers
At this point there is maximal overlap thick and thin filaments
What are the 2 other length-dependent mechanisms in cardiac muscle that alter tension developed?
- increasing muscle length increases the Ca2+ sensitivity to troponin C
- increasing muscle length increases Ca2+ release form the sarcoplasmic reticulum
The length-tension relationship for single myocardial cells can be extended to a length-tension relationship for the _____.
ventricles
The length of a single ventricular muscle fiber just prior to contraction corresponds to left ventricular _____ volume
end-diastolic
Why do cardiac muscle fibers not operate over their entire length-tension curve?
Because it has a high resting tension, and small increases in length produce large increases in resting tension
What is preload?
The resting length from which the muscle contracts
Preload is equal to what?
left ventricular end-diastolic volume
The relationship between preload and developed tension is based on what?
The degree of overlap of thick and thin filaments
The afterload for the left ventricle is what?
aortic pressure
When is the velocity of shortening of cardiac muscle maximal?
When afterload is zero
Velocity of shortening decreases as afterload _____.
increases
What are the 3 parameters in which the function of the ventricles are described?
- stroke volume
- ejection fraction
- cardiac output
What is stroke volume?
The volume of blood ejected on one ventricular contraction
Stroke volume is the difference between what 2 values?
The volume of blood in the ventricle before ejection and the volume remaining in the ventricle after ejection
Stroke volume is typically about __ mL
70 mL
What is ejection fraction?
the fraction of the end-diastolic volume that is ejected in one stroke
What is ejection fraction normally?
55%
What is the ejection fraction an indicator for?
contractility
An increase in contractility results in ____ in ejection fraction.
A decrease in contractility results in _____ in ejection fraction
increases
decreases
What is cardiac output?
The total volume of blood ejected per unit time
Cardiac output is depends on what 2 values?
stroke volume and heart rate
What is normal cardiac output?
5000 mL/min
What does the Frank-Starling relationship state?
That the volume of blood ejected by the ventricle depends on the volume present in the ventricle at the end of diastole, which correlates with venous return
What does the Frank-Sterling law of the heart ensure?
that cardiac output equals venous return
As venous return increases, what 2 other things increase?
end-diastolic volume and stroke volume
Positive inotropic agents produce _____ in stroke volume and cardiac output for a given end-diastolic volume.
increases
What is the end result of positive inotropic agents?
A larger fraction of the end-diastolic volume is ejected per beat and there is an increase in ejection fraction
Negative inotropic agents produce _____ in stroke volume and cardiac output for a given end-diastolic volume.
decreases
What is the end result of negative inotropic agents?
A smaller fraction of the end-diastolic volume is ejected per beat and there is a decrease in ejection fraction
What does the ventricular pressure-volume loop describe?
One complete cycle of ventricular contraction, ejection, relaxation and filling
The isovolumetric contraction occurs between what 2 points on the ventricular pressure-volume loop?
Begins at point 1, which marks the end of diastole. And ends at point 2, which is when the ventricle is activated, it contracts, and ventricular pressure increases dramatically
Left ventricular pressure _____ and left ventricular volume _____ between points 1 and 2 on the ventricular pressure-volume loop
increases
remains the same
The ventricular ejection occurs between what 2 points on the ventricular pressure-volume loop?
Begins at point 2, which is the point at which ventricular pressure surpasses aortic pressure, forcing the aortic valve to open. Ends at point 3. During the 2 points blood is rapidly ejected, driven by the pressure gradient between the left ventricle and the aorta
Left ventricular pressure _____ and left ventricular volume _____ between points 2 and 3 on the ventricular pressure-volume loop
remains high
decreases dramatically
The volume remaining in the ventricle at point 3 is the end-_____ volume
systolic
End-systolic volume is approximately __ mL.
70 mL
The width of the ventricular pressure-volume loop is equal to what?
the volume of blood ejected, or the stroke volume
The isovolumetric relaxation occurs between what 2 points on the ventricular pressure-volume loop?
Begins at point 3, in which systole ends and the ventricle relaxes because ventricular pressure decreases below aortic pressure and the aortic valve closes. Ends at point 4, which is the point at which ventricular pressure is less than left atrial pressure
Left ventricular pressure _____ and left ventricular volume _____ between points 3 and 4 on the ventricular pressure-volume loop
decreases rapidly
remains constant
Ventricular filling occurs between what 2 points on the ventricular pressure-volume loop?
Begins at point 4, which is the point in which ventricular pressure is less than left atrial pressure, causing the mitral valve to open. 1, which is the point in which the left ventricle has been filled with blood (end-diastolic)
Left ventricular pressure _____ and left ventricular volume _____ between points 4 and 1 on the ventricular pressure-volume loop
increases slightly (due to the compliance of the ventricles)
increases back to end-diastolic volume (=140 mL)
What 3 changes can alter the ventricular pressure-volume loop?
- increased preload
- increased afterload
- increased contractility
How does an increased preload alter the ventricular pressure-volume loop?
Stroke volume, which is measured by the width of the pressure-volume loop, increases
How does an increased afterload alter the ventricular pressure-volume loop?
Less blood is ejected from the ventricle during systole, which results in decreased stroke volume and increased end-systolic volume
How does increased contractility alter the ventricular pressure-volume loop?
The ventricle can develop greater tension and pressure during systole and eject a larger volume of blood than normal. Therefore stroke volume increases and end-systolic volume decreases
