Cardiac Muscle-Control of Myocardial Contraction

Question 1

What is twitch?

Answer 1

the force/contraction of muscle

Question 2

What happens to the force during a cardiac AP?

Answer 2

it rises and peaks at 200ms then falls during relaxation

Question 3

What is the source of activator calcium in cardiac muscle?

Answer 3

1. DHPR/L type calcium channels that allow calcim to enter the cell from extracellular space
2. Sarcoplasmic reticulum whose ryanodine receptors respond to initial inflow of calcium and release more calcium

Question 4

Is the lumen of a t-tubule intra or extracellular?

Answer 4

extracellular

Question 5

What pumps are responsible for recovery from calcium release in cardiac myocytes?

Answer 5

1. ATP-calcium pump in SR (removes 2/3 calcium to SR) aka srca
2. 3Na-1Ca exchanger removes 1/3 of calcium to ECS –> electrogenic

Question 6

Why does cardiac muscle become stiff during ischemia or excess calcium?

Answer 6

ATP is required for recovery/repolarization of cells

Question 7

Why does cardiac muscle stop beating if removed from calcium media but skeletal muscle continues?

Answer 7

cardiac muscle derives activator calcium from both SR and ECS –> calcium induced calcium release whereas skeletal muscle only derives activator calcium from SR

Question 8

Does AP duration control twitch duration in cardiac and skeletal muscle?

Answer 8

only in cardiac muscle

Question 9

What is the difference between SR calcium release in cardiac vs skeletal muscle?

Answer 9

ryanodine receptor in skeletal muscle is voltage gated via a direct connection with the DHPR receptor whereas it is calcium gated in cardiac muscle

Question 10

What prevents myosin from binding actin in muscle?

Answer 10

tropomyosin blocks actin binding site b/c of troponin i subunit –> only moves once troponin c is bound by calcium

Question 11

What is the fastest and most important pacemaking mechanism in the heart?

Answer 11

SA node –> under influence of hormones, etc.

Question 12

3 ways to change heart rate

Answer 12

1. change rate of phase 4 diastolic depolariation
2. maintain a different negative threshold
3. reach a more different maximum diastolic potential

Question 13

What are the effects of sympathetic stimulation of the SA node?

Answer 13

1. last part of diastolic depolarization is accelerated/increased rate of depolarization by increasing conductance of t-type calcium channels
2. increased overshoot of the action potential because of increased Ica
3. more negative maximum diastolic potential
4. increased activity of Na/K ATPase leading to faster recovery

Question 14

What is the predominant control point in SA node pacing?

Answer 14

diastolic interval because it is more sensitive than the AP duration to regulatory influence

Question 15

What is a positive chronotropic effect?

Answer 15

the increase in heart rate due to catecholamines like norepi/epi

Question 16

Sympathetic agonists on heart receptors are classified as _______ and are antagonized by blockers such as _____.

Answer 16

beta adrenergic and propanolol

Question 17

How do beta agonists mediate their effect on cardiac cells?

Answer 17

1. g protein coupling –> adenylyl cyclase- -> cAMP –> cAMP PKA–> phosphorylation of calcium channel –> increase Ica
2. 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
3. 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

Question 18

What enzyme removes cAMP from the cell during a g-cascased?

Answer 18

phosphodiesterase breaks down cAMP and phosphatases dephosphorylate calcium channel and beta and gamma subunits of g protein bind to alpha again

Question 19

T/F there is always parasympathetic vagal tone in the heart

Answer 19

T

Question 20

How is parasympathetic action on the SA node mediated?

Answer 20

1. ACh binds to muscarinic receptor (G protein) leading to direct activation of Ik(ach) which makes membrane potential more negative, thus lowering heart rate
2. ACh also has a Gi effect on the cyclase pathway and inhibits adenylyl cyclase, thereby reducing Ica –> reciprocal action against sympathetic

Question 21

At high vagal stimulation rates, is the K current sufficient to halt the pacemaker potential?

Answer 21

yes

Question 22

How are soluble second messengers involved in the ACh effect on potassium current?

Answer 22

they are not –> direct g-protein switch

Question 23

3 ways to control strength of cardiac contraction

Answer 23

1. increase amount of calcium (usually not saturated (shift along pca tension curve)
2. altered affinity to calcium (left shift in pca tension curve)
3. altered strength of contraction for a given amount of bound calcium via more myofibrils or structural change (upward shift of pca tension curve)

Question 24

Why does the heart have to beat stronger as it beats faster?

Answer 24

less diastolic filling interval + increased venous return requires more blood to be propelled in each beat

Question 25

What is the rate staircase?

Answer 25

intrinsic control mechanism of the heart: faster the muscle is stimulated, the stronger the heart contraction

Question 26

At higher heart rates are AP longer or shorter?

Answer 26

shorter and contraction is higher and relaxation is faster –> duration of contraction is partially controlled by duration of AP

Question 27

What happens to systolic and diastolic timing as heart rate increases?

Answer 27

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

Question 28

What is the phenomenon of post extra systolic potentiation?

Answer 28

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

Question 29

How does the heart respond to stretch during diastolic filling?

Answer 29

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

Question 30

Why does cardiac muscle have a steeper passive length tension curve than skeletal muscle?

Answer 30

increased resting elasticity is due to shorter titin and connective tissue around myocytes –> heart stretches in response to passive filling aka diastolic filling

Question 31

What is the importance of a steeper active length tension curve for cardiac muscle vs skeletal muscle?

Answer 31

small changes in sarcomere length/stretch results in large changes in tension/twitch

Question 32

When cardiac muscle is stretched, myofilaments become farther apart/closer together and more/less sensitive to calcium.

Answer 32

closer together and more sensitive –> stronger higher twitch strength (pca tension curve is shifted to left at high sarcomere length)

Question 33

Effect on cardiac twitch of: elevated extracellular calcium

Answer 33

higher force

Question 34

Effect on cardiac twitch of: elevated extracellular potassium

Answer 34

shorter action potential, lower conducting velocity, less negative resting potential (which causes na inactivation)–> reduced strength of contraction

Question 35

Effect on cardiac twitch of: reduced extracellular sodium

Answer 35

lowered na reduces the electrochemical energy gradient across the membrane which reduces na-ca exchange –> ca accumulates in cell and increases strength of twitch

Question 36

How does ACh shorten cardiac AP?

Answer 36

increased K+ permeability –> reduced plateau time –> decreased strength of contraction + rate saircase + decreased cAMP and vagal tone to reduce sympathetic drive

Question 37

What is the proposed mechanism for heart failure?

Answer 37

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