Cardiac Muscle Contraction

Question 1

What structures in cardiac cells invaginate at the z-line?

Answer 1

T-tubules

Question 2

In cardiac cells, the appearance of action potentials trigger both ______ release from out side the cell and from the SR, which results in the contraction of the sarcomere

Answer 2

Calcium

Question 3

Explain the process of Calcium-Induced Calcium Release (CICR)

Answer 3

It is the process by which cardiac muscle cells open the Ryanodine receptors. During an AP, a small amount of Ca2+ influx through L-type Ca2+ channels binds the Ryanodine receptor on the SR and causes them to open, which allows large amounts of Ca2+ to flow out into the sarcoplasm and leading to muscle contraction

Question 4

T/F: The cardiac AP is Na+ dependent and allows Na+ entry into the myofiber

Answer 4

False, the cardiac AP is Ca2+ dependent and allows Ca2+ entry into myofiber

Question 5

Can APs experience summation? Why or why not?

Answer 5

Cardiac APs are much longer than muscle APs, and their refractory periods prevent summation, therefore the heart contracts ONLY by twitch

Question 6

What occurs during the 4 phases of cardiac AP?

Answer 6

Phase 0: depolarization by Na+ channels rapidly opening corresponding to the initial spike seen
Phase 1: Initial stage of repolarization triggered by closing Na+ channels
Phase 2: Plateau stage where rate of repolarization is slowed by the influx of Ca2+ ions into the cell
Phase 3: Later stage of repolarization
Phase 4: Occurs after repolarization is complete

Question 7

Which phase during the cardiac AP does Ca2+ influx occur?

Answer 7

Phase 2

Question 8

Which phases of the cardiac AP correspond to the absolute refractory period?

Answer 8

Phase 1 and 2

Question 9

What type of channel blockers are cardiomyocytes sensitive to?

Answer 9

L-type Ca2+ channels (these are the gates to CICR)

Question 10

What is meant by electrotonic propagation?

Answer 10

The movement of charges (charge displacement) through gap junctions between adjacent cells that result from the flow of an AP…this is how APs propagate throughout cardiac tissue

Question 11

External Ca2+ entry contributes what % of total Ca2+ elevation and through which channels does it enter the cell?

Answer 11

Contributes ~20% of total calcium and it enters through L-type

The other 80% is through calcium induced calcium release (CICR) through ryanodine receptors in the SR

Question 12

T/F: As in skeletal muscle, ryanodine receptors in cardiac muscle are physically coupled with L-type channels

Answer 12

False, RyR are NOT physically attached in cardiac cells, they are located on the SR and are sensitive to Ca2+ and trigger CICR

Question 13

What are the main Ca2+ clearance mechanisms and what % of total Ca2+ are removed by each?

Answer 13

1. SERCA (uses ATP hydrolysis to pump Ca2+ back into SR) accounts for ~80%
2. NCX- Na+/Ca2+ exchanger that expels 1 Ca2+ for every 3 Na+ in and accounts for ~15%
3. PMCA ~5%

Question 14

T/F: Cardiac muscle recruitment can increase the force of contractions, similar to what is seen in muscle cells

Answer 14

False, recruitment does not occur in cardiac cells

Question 15

Heart rate is increased by _______ activation and the release of which NT?

Answer 15

sympathetic activation release norepinephrine which increases HR

Question 16

What is the function of parasympathetic vagal nerve in the establishment of resting heart rate?

Answer 16

The SA node is spontaneously active and triggers and endogenous heart rate of about 100 bpm, this is normally reduced under influence of the parasympathetic vagal nerve (ACh release) to about 60 bpm

Question 17

What is meant by a “change in contractility”?

What effect will a change in contractility have on a length-tension curve?

Answer 17

A change contractility means that for any initial length the active tension developed at that length will be greater. A classic example of a change in contractility in heart is due to norepinephrine.

Change in contractility will shift the length tension curve UP

Question 18

Cardiac muscle exhibits an increase in active tension with increasing initial length due to what?

Answer 18

An increase in sensitivity. This is the basis of the Frank Starling law of cardiac function. Stretching the cardiac muscle increases the active tension produced because the sensitivity of the muscle to stimulation is greater. Calcium levels do not change as function of stretch, instead the TroponinC is believed to increase its affinity for calcium, with greater initial length. This increase in calcium affinity means that the same amount of calcium now causes greater TroponinC activity and tropomyosin movement from the myosin binding sites on the thin filament.

Question 19

Phospholamban is a protein that inhibits SERCA, the sarcoplasmic reticulum Ca2+ ATPase. A drug that inhibits phosphlamban function would be expected to:

Answer 19

Shorten the duration of the cardiac twitch.
Phospholamban normally puts the brake on SERCA, slowing calcium clearance from the sarcoplasm. However drugs or epinephrine can lead to inhibition of phospholamban removing the brake from SERCA, leading to more rapid and more complete clearance of sarcoplasmic calcium at the end of the twitch. This rapid relaxation shortens the duration of the cardiac twitch, allowing for a shorter refractory period, and higher heart rates if needed.

Question 20

In a curve that plots cardiomyocyte tension on the y-axis and sarcoplasmic calcium levels on the x-axis, a shift of the curve upward represents what?

Answer 20

It represents an increase in sensitivity.
In a calcium vs. tension curve (note: this is not a length tension curve), a shift of the curve upward means that any given sarcoplasmic calcium level (x-axis) more tension is produced (y-axis). This means that the sarcomere is now more sensitive to a given amount of calcium. In contrast, increased contractility is represented by movement along the original curve. Specifically increasing sarcoplasmic calcium levels produce more tension.