Cardiac Muscle-Control of Myocardial Contraction Flashcards
What is twitch?
the force/contraction of muscle
What happens to the force during a cardiac AP?
it rises and peaks at 200ms then falls during relaxation
What is the source of activator calcium in cardiac muscle?
- DHPR/L type calcium channels that allow calcim to enter the cell from extracellular space
- Sarcoplasmic reticulum whose ryanodine receptors respond to initial inflow of calcium and release more calcium
Is the lumen of a t-tubule intra or extracellular?
extracellular
What pumps are responsible for recovery from calcium release in cardiac myocytes?
- ATP-calcium pump in SR (removes 2/3 calcium to SR) aka srca
- 3Na-1Ca exchanger removes 1/3 of calcium to ECS –> electrogenic
Why does cardiac muscle become stiff during ischemia or excess calcium?
ATP is required for recovery/repolarization of cells
Why does cardiac muscle stop beating if removed from calcium media but skeletal muscle continues?
cardiac muscle derives activator calcium from both SR and ECS –> calcium induced calcium release whereas skeletal muscle only derives activator calcium from SR
Does AP duration control twitch duration in cardiac and skeletal muscle?
only in cardiac muscle
What is the difference between SR calcium release in cardiac vs skeletal muscle?
ryanodine receptor in skeletal muscle is voltage gated via a direct connection with the DHPR receptor whereas it is calcium gated in cardiac muscle
What prevents myosin from binding actin in muscle?
tropomyosin blocks actin binding site b/c of troponin i subunit –> only moves once troponin c is bound by calcium
What is the fastest and most important pacemaking mechanism in the heart?
SA node –> under influence of hormones, etc.
3 ways to change heart rate
- change rate of phase 4 diastolic depolariation
- maintain a different negative threshold
- reach a more different maximum diastolic potential
What are the effects of sympathetic stimulation of the SA node?
- last part of diastolic depolarization is accelerated/increased rate of depolarization by increasing conductance of t-type calcium channels
- increased overshoot of the action potential because of increased Ica
- more negative maximum diastolic potential
- increased activity of Na/K ATPase leading to faster recovery
What is the predominant control point in SA node pacing?
diastolic interval because it is more sensitive than the AP duration to regulatory influence
What is a positive chronotropic effect?
the increase in heart rate due to catecholamines like norepi/epi
Sympathetic agonists on heart receptors are classified as _______ and are antagonized by blockers such as _____.
beta adrenergic and propanolol
How do beta agonists mediate their effect on cardiac cells?
- g protein coupling –> adenylyl cyclase- -> cAMP –> cAMP PKA–> phosphorylation of calcium channel –> increase Ica
- cAMP also causes phosphorylation of phospholamban leading to increased uptake of Ca to SR –> increases pool of calcium in SR –> faster relaxation of muscle and increased calcium release on each beat
- change in affinity of troponin I allows calcium to dissociate faster –> reduced affinity for calcium –> shifts pca tension curve to right –> decrease duration of contraction
though these effects are antagonistic, together, because of the curve shift, actually results in an increase in force and decrease in duration
What enzyme removes cAMP from the cell during a g-cascased?
phosphodiesterase breaks down cAMP and phosphatases dephosphorylate calcium channel and beta and gamma subunits of g protein bind to alpha again
T/F there is always parasympathetic vagal tone in the heart
T
How is parasympathetic action on the SA node mediated?
- ACh binds to muscarinic receptor (G protein) leading to direct activation of Ik(ach) which makes membrane potential more negative, thus lowering heart rate
- ACh also has a Gi effect on the cyclase pathway and inhibits adenylyl cyclase, thereby reducing Ica –> reciprocal action against sympathetic
At high vagal stimulation rates, is the K current sufficient to halt the pacemaker potential?
yes
How are soluble second messengers involved in the ACh effect on potassium current?
they are not –> direct g-protein switch
3 ways to control strength of cardiac contraction
- increase amount of calcium (usually not saturated (shift along pca tension curve)
- altered affinity to calcium (left shift in pca tension curve)
- altered strength of contraction for a given amount of bound calcium via more myofibrils or structural change (upward shift of pca tension curve)
Why does the heart have to beat stronger as it beats faster?
less diastolic filling interval + increased venous return requires more blood to be propelled in each beat
What is the rate staircase?
intrinsic control mechanism of the heart: faster the muscle is stimulated, the stronger the heart contraction
At higher heart rates are AP longer or shorter?
shorter and contraction is higher and relaxation is faster –> duration of contraction is partially controlled by duration of AP
What happens to systolic and diastolic timing as heart rate increases?
diastolic filling time decreases but twitch remains mostly the same –> systole/diastolic ratio increases –> less calcium efflux (during diastole) occurs relative to calcium influx (during systole) –> higher calcium concentration in cell –> higher force of contraction
What is the phenomenon of post extra systolic potentiation?
during steady series of contractions, a premature beat/extra systole is usually smaller in force but the subsequent few contractions are enhanced –> rhythm affects calcium release
How does the heart respond to stretch during diastolic filling?
per starling law, the force in myocytes increases in response to increased elastic expansion of heart AKA if more blood returns to heart and expands it, force has to increase to ensure stroke volume is maintained
Why does cardiac muscle have a steeper passive length tension curve than skeletal muscle?
increased resting elasticity is due to shorter titin and connective tissue around myocytes –> heart stretches in response to passive filling aka diastolic filling
What is the importance of a steeper active length tension curve for cardiac muscle vs skeletal muscle?
small changes in sarcomere length/stretch results in large changes in tension/twitch
When cardiac muscle is stretched, myofilaments become farther apart/closer together and more/less sensitive to calcium.
closer together and more sensitive –> stronger higher twitch strength (pca tension curve is shifted to left at high sarcomere length)
Effect on cardiac twitch of: elevated extracellular calcium
higher force
Effect on cardiac twitch of: elevated extracellular potassium
shorter action potential, lower conducting velocity, less negative resting potential (which causes na inactivation)–> reduced strength of contraction
Effect on cardiac twitch of: reduced extracellular sodium
lowered na reduces the electrochemical energy gradient across the membrane which reduces na-ca exchange –> ca accumulates in cell and increases strength of twitch
How does ACh shorten cardiac AP?
increased K+ permeability –> reduced plateau time –> decreased strength of contraction + rate saircase + decreased cAMP and vagal tone to reduce sympathetic drive
What is the proposed mechanism for heart failure?
abnormal ca release via ryr channels resulting in impaired ca cycling–> chronic hyperactivity of sympathetic system during heart failure (compensative) –> pka hyperphosphorylation of cardiac ryr which destabilizes it –> increased ca leak during diastole –> depleted stores –> cardiac arrhythmia
