Excitation Contraction Coupling Cardia Cycle Flashcards
What happens when you add increasing doses of Diltiazem (a Ca channel blocker) to a cell?
Ca channels that open during phase 2 are blocked → plateau phase of AP gets shorter → contraction of muscle gets increasingly shorter
What is Ca that comes in during the plateau phase important to?
Contraction of cardiac muscle
What happens to the twitch force of a cell when you add increasing doses of Diltiazem?
It decreases
Define: sarcolemma
outer-cell membrane
Define: T-tubule
invagination of cell membrane that goes deep in muscle and communicates with EC space.
How does the AP open Ca channels along the membrane?
AP travels along the cardiac muscle and down the T-tubule when the cardiac muscle depolarizes → Ca channels open along the membrane
Where is Ca stored inside the cell?
Sarcoplasmic reticulum
When do Ca Channels open?
when there is a voltage change between -10 mV and +10 mV
What is the main mechanism for getting Ca from the cytosol back into the SR?
ATPase pump
How does extracellular Ca aid in muscle contraction?
Ca channel opens → Ca flows in → Ca binds to rhyinadine channels → allows Ca to flow from SR into cytoplasm → intracellular Ca concentration increases → contraction
How does the membrane voltage increase from -10 mV to 10 mV?
Fast sodium channels open
How do Catecholamines function in muscle contraction?
E or NE bind β1 receptor → causes activation of adenylyl cyclase → increases cyclic AMP → stimulates cAMP-PK → Phosphorylates Phospholamban and Troponin → enhance relaxation of muscle
What happens when phospholamban is phosphorylated?
it decreases inhibition → enhances activity of Ca pump → pumps Ca back into SR faster
What is phospholamban?
Regulatory protein that inhibits Ca pump
What happens when Troponin I is phosphorylated?
it has reduced affinity for Trp C for Ca → Ca still binds but not as tightly → Ca is releases from Troponin more quickly
How do catecholamines affect the cardiac muscle?
It makes them more efficient in handling Ca → more efficient in contracting, creating pressure, and pumping out greater SV
What happens when a Ca channel is phosphorylated?
It stays open longer and conducts more Ca → more efficient contraction b/c more Ca in cell
What does the Ca pump do to the cardiac muscle cell?
it uses ATP to remove Ca from the cytosol and put it in the EC
What does the Na-Ca exchanger pump do to the cardiac cell?
It removes Ca from the cell by exchanging 3 Na for 1 Ca
What do Cardiac Glycosides do to cardiac muscle cells?
they inhibit Na-K pump which results in intracellular Na+ accumulation
What is the resulting effect of a Cardiac glycoside?
Na concentration outside cell decreases
less sodium gradient to exchange Na for Ca
more calcium in cell
Increased calcium in cell promotes a better contraction in the ventricle
dont enhance relaxation
Define: Systole
Contraction and shortening
Define: Diastole
Relaxation and refilling
move calcium back into storage
What is the equation for Cardiac Output?
CO = HR X SV
How can you increase HR using the autonomic nervous system?
by stimulating sympathetic nervous system
How does Ca cycling influence SV?
it increases it
What governs the systolic phase of Ca cycling?
AP (depolarization in the heart) → Ca channels open, firing of SA node causes depolarization
In general, how does Ca effect muscle contraction?
Ca binds to Troponin C → troponin moves and uncovers myosin binding site → myosin binds to actin → shortening occurs → contraction
What effect does ACh have on the contractile force of the heart?
Decrease HR
Decrease force of contraction
Decrease SV by reducing Contraction
What effect does NE have on the contractile force of the heart?
Increases contractile force
increases SV
What is the mechanism behind Calcium induced Calcium release?
Ca ions bind to a channel protein on SR, opening a channel and allows Ca out of storage into cytoplasm
What increases SV?
Contractility
Preload
How does afterload effect SV?
it reduces it
How do contractility and Preload effect CO?
they increase ut
What does afterload do to CO?
limits CO
What happens to SV as you increase afterload?
it inhibits SV
Define: Preload
the force present in a relaxed muscle (measure of how close you are to optimal length)
Define: Optimal Length (Lo)
length at which you get max contraction in skeletal muscle
get max shortening
is preload fixed in the heart?
no
What determines Preload in vitro?
it varies with resting length of muscle
What determines Preload in vivo?
venous pressure and end diastolic volume
Define: End Diastolic Volume (EDV)
amount of blood in ventricle at end of filling phase
What determines preload?
amount of blood that fills ventricles prior to being stimulated to contract
What does the preload force set?
the length of the resting muscle
Why does cardiac muscle operate at less than its optimal legth?
the more it is filled the better it contracts until it gets to a certain length
if you over stretch it, function starts to drop off
Define: Frank-Starling Relationship
The sequential increase in output by putting more blood in the ventricle
What happens as more preload is added to the ventricle?
The ventricle will contract more efficiently
Define: Afterload
The force exerted by a shortening muscle (force that opposes shortening of muscle)
(i.e. the weight you hold)
What is the afterload of the right ventricle?
pulmonary artery
What is the afterload of the Left Ventricle?
aorta
How is afterload determined in vitro?
by the applied load
How is afterload determined in vivo?
by arterial pressure
(systemic arterial pressure for the left ventricle (aorta) and pulmonary arterial pressure for the right ventricle
What does the RV empty its blood contents?
When it overcomes the pressure of pulmonary artery to open the pulmonic valve
What does the LV empty its blood contents?
when it overcomes the pressure of the aorta to open the aortic valve
Define: Contractility (Inotropy)
The variable state of muscle performance at a given muscle length
The ability to increase cardiac function not dependent on length
What do most pathways that regulate contractility involve?
Ca++
what is the relationship between contractility, length, and preload?
Contractility is independent of length and preload
What is the result of contractility being independent of length and preload?
no matter what the preload of a muscle is at, the max velocity of shortening comes back to the same point
no matter what the length of your muscle is stretched to, if you increase contractility, you can make muscle contract more efficiently
what is contractility distinguished from in muscle performance?
length-dependent changes
How do you increase contractility?
increase Ca content
What happens to SV if you increase contractility?
it increases
What is contractility determined by?
dP/dt
(rate at which pressure increases)
Define: Chronotrope
anything that effects heart rate
Define: Positive Chronotrope
increases heart rate
(sympathetic nervous system stimulation [release of NE or E])
Define: Negative Chronotrope
decreases heart rate
(ACh → binds muscarinic receptor)
Define: Inotrope
influences contractility
Define: Positive inotrope
increases contractility
(NE, E bind β1 receptors and enhance Ca cycling
Define: Negative Inotrope
Decreases contractility → ACh
What is parasympathetic (chronotrope/inotrope)?
Negative Chronotrope
Negative Inotrope
What is sympathetic (chronotrope/inotrope)?
positive chronotrope
positive inotrope
Equation: Ejection Fraction
EF = EDV - (ESV/EDV) → EF = SV/EDV
Define: Ejection Fraction
% of blood in ventricle that gets ejected each time heart beats
(ratio of the volume of blood ejected from LV per beat (SV) to the volume of blood in the LV at the end of diastole (EDV)
Define: End diastolic volume (EDV)
max volume in ventricle prior to contraction
Which one of the following would most likely occur as a direct result of applying a Ca++ channel blocker to a ventricular myocyte?
A. no effect
B. An increase in contractility
C. an increase in HR
D. a reduction in the duration of phase 2 of the action potential
E. Loss in phase 1 of the action potential
D. a reduction in the duration of phase 2 of the action potential
In contracting calcium muscle, calcium…
A. is present in an amount that usually saturates all intracellular calcium binding sites
B. comes from both the extracellular space and from the SR
C. enters the cell during the rapid upstroke (phase 0) of the AP
D. all of the above
E. none of the above
comes from both the extracellular space and from the SR
The Frank-Starling Relationship…
A. Explains the effect of ACh on ventricular performance
B. Explains the relationship between afterload (wall stress) and maximum +dP/dt
C. Is determined during isovolumic contraction
D. Explains the influence of positive inotropic agents on cardiac function
E. None of the above
E. None of the above
