12/5/2014 Medical Physiology Cardiac Muscle Mechanics Eric Olson

Question 1

T/F: Cardiac muscle is similar to striated skeletal muscle and shows A and I bands.

Answer 1

True

Question 2

What structure separated adjacent cardiac myocytes?

Answer 2

Intercalated disc

Question 3

What cell linkages are found at intercalated discs?

Answer 3

Gap junctions (and desmosomes)

Question 4

Do T-tubules exist in cardiac muscle?

Answer 4

Yes, and they invaginate along the Z line.

Question 5

Why is cardiac muscle called a functional syncytium?

Answer 5

Because even though cardiac muscle cells are uninucleate or binucleate, the presence of gap junctions allows all cardiac muscle cells to act as a unit. The syncytium can be split into two syncytia: atrial and ventricular

Question 6

Cardiac muscle has abundant reserves of ___ to store oxygen to aid in aerobic metabolism.

Answer 6

Myoglobin

Question 7

Does cardiac muscle maintain energy reserves?

Answer 7

Yes, in the form of glycogen and lipid inclusions.

Question 8

How are ryanodine receptors opened in cardiac muscle (different from skeletal muscle)?

Answer 8

Calcium-induced calcium release (CICR)

Question 9

What is Calcium-induced calcium release (CICR)?

Answer 9

In a cardiomyocyte AP, a small amount of calcium influx through the L-type calcium channel binds to the ryanodine receptors in the SR, and the SR opens releasing a ton of calcium.

Question 10

What are the differences between skeletal and cardiac (ie ventricular) AP?

Answer 10

1. Timing: Cardiac AP is ~250ms, whereas skeletal AP is ~5ms
2. Length: No summation in cardiac muscle (twitch only)
3. Cardiac AP is calcium-dependent, skeletal AP is sodium-dependent.

Question 11

What are the Phases (0 to 4) of the cardiac (ie ventricular in this case) AP?

Answer 11

1. Phase 0 - Na+ depolarization, cell potential goes from -85mV to +30mV.
2. Phase 1 - Initial phase of repolarization
3. Phase 2 - Plateau stage
4. Phase 3 - Repolarization completes
5. Phase 4 - After repolarization is complete

Question 12

What is Phase 1 of the cardiac AP stimulated by?

Answer 12

Closing of the Na channels

Brief activation of transient inward current (I-to)

Question 13

What happens during Phase 2 of the cardiac AP?

Answer 13

Rate of repolarization of slowed by influx of Ca ions.
Ca current in
K current out

Question 14

What happens during Phase 3 of the cardiac AP?

Answer 14

K ions out

Question 15

What cells do not have Phase 4 as part of their cardiac AP?

Answer 15

Any cells that have endogenous pacemaker activity, ie SA node.

Question 16

Calcium coming in through L-type calcium channels contributes how much to the twitch?

Answer 16

It is 20% of the calcium needed for twitch.

Question 17

T/F: In cardiac muscle, ryanodine receptors on the SR are physically coupled to L-type calcium channels.

Answer 17

False. This is how it is in skeletal muscle only. Cardiomyocytes use CICR.

Question 18

T/F: In the depolarized (ie Phase 2) stage of the cardiac AP< the sodium-calcium ATPase exchanges (NTX) can “work in reverse” letting into the cell 1 calcium for 3 sodiums out.

Answer 18

True, but this is not the main source of calcium.

Question 19

What is SERCA?

Answer 19

Sarcoplasmic and endoplasmic reticulum ATPase that pumps Ca back into the SR during repolarization. This is the main way the Ca is cleared.

Question 20

Because of the trans-sarcolemmal influx of calcium, cardiac muscle is much more sensitive to _____ than is skeletal muscle, and therefore cardiac muscle is also more sensitive to L-type calcium channel blockers.

Answer 20

Extracellular calcium

Question 21

How does CICR work w/r/t ryanodine receptors?

Answer 21

Calcium binds the ryanodine receptor, it opens, more calcium comes in, binds neighboring ryanodine receptors etc. etc., like a domino effect

Question 22

Cardiac muscle contraction works like skeletal muscle contraction in that calcium binds to ____ which leads to the movement of tropomyosin off the myosin binding sites on the thin filament.

Answer 22

Troponin C

Question 23

T/F: Myosin heavy chains in cardiac and skeletal muscle are of the same type.

Answer 23

False. Myosin heavy chains in cardiac muscle are different than in skeletal muscle.

Question 24

What process is used in skeletal muscle but not cardiac muscle to increase the force of contraction?

Answer 24

Recruitment. *NOT used in cardiac muscle.

Question 25

Without parasympathetic innervation, the SA node HR is about how many BPM?

Answer 25

100. The vagus nerve (ACh release) adjusts it to about 60 BPM.

Question 26

What is the basis for the Frank-Starling Law of the Heart?

Answer 26

The force of contraction increases at increased end-diastolic length.

Question 27

The Frank-Starling Law of the Heart states:

Answer 27

The more the ventricle is filled with blood during diastole, the greater the volume of ejected blood will be during the resulting systolic contraction. This is NOT based on thick nd thin filament overlap, only on the LOAD of the blood on the muscle fiber.

Question 28

Increased load stretched the myocardium and increases the affinity of troponin C for __1__, leading to an increase in contractile force for a given level of sarcoplasmic calcium.. This is called an increase in __2__.

Answer 28

1. Calcium

2. Sensitivity

Question 29

What is the muscle-definition of preload?

Answer 29

The initial sarcomere length

Question 30

The force that any single muscle fiber generates is proportional to the initial sarcomere length (aka preload) OR, equivilantly:

Answer 30

the end-diastolic volume of the ventricle

Question 31

In the human heart, maximal force is generated with an initial sarcomere length of?

Answer 31

2.2 micrometers

Question 32

Troponin C’s affinity for calcium has the effect of more formation of what?

Answer 32

Crossbridges per AP (lead to greater force of systolic contraction)

Question 33

Give an example of an inotropic agent.

Answer 33

Norepinephrine

Question 34

Norepinephrine has what effect on cardiac muscle?

Answer 34

More calcium released from SR –> Increased contractility

Question 35

After administration, how many beats does it take for the amplitude of the AP to increase?

Answer 35

None, It happens immediately.

Question 36

After administration, how many beats does it take for the tension (in grams) of the heart to increase?

Answer 36

About 8 beats. AP increases immediately, but the rise in intracellular calcium needs to catch up.

Question 37

Positive inotropic agents such as norepinephrine have 2 specific effects on cardiac muscle activity. What are they?

Answer 37

1. Increase contractility
2. Curve of tension vx time becomes both higher AND steeper, meaning the twitch length is shorter (systole is shorter) –> higher HR while diastolic filling is maintained.

Question 38

In beta-adrenergic stimulation, is norepinephrine, the increase in cAMP leads to increased intracellular calcium and what?

Answer 38

Activation of a protein kinase which phosphorylated a protein called Phospholamban.

Question 39

What is the effect of activated phospholamban?

Answer 39

Increased sensitivity of SR Ca pump, meaning faster repolarization (AP duration shorter). (Positive inotropic and chronotropic effects)

Question 40

Tension is absent at what concentration of sarcoplasmic calcium in both smooth and cardiac muscle?

Answer 40

100 nM

Question 41

Tension is at a maximum value at 10 uM concentration of sarcoplasmic calcium in what muscle?

Answer 41

BOTH smooth and cardiac muscle

Question 42

Changes in contractility shift the _____-tension curve upward.

Answer 42

Length (increase in contractility due to increased entry of Ca)

Question 43

Can administration of norepinephrine change the tension/load of cardiac muscle without changing the length of the muscle?

Answer 43

Yes, the length-tension curve stays the same shape, but shifts upward to reflect the additional tension produced (see page 364-365 of notes). This is isometric tension.

Question 44

Does norepinephrine administration change the work performed by cardiac muscle?

Answer 44

Yes, the length can change at a given load + NE admin.

Question 45

What is the maximal length-tension curve?

Answer 45

Just a way of saying that on a curve of tension vs length, at some point the muscle cannot shorten anymore despite the load being put on it. It is capped at 12 mm control and 11 mm with NE admin, for example.