Excitation/Contraction Coupling Flashcards Preview

Cardiovascular > Excitation/Contraction Coupling > Flashcards

Flashcards in Excitation/Contraction Coupling Deck (35):
1

key features of cardiac muscle

large T-tubules

cell to cell electrical connections (gap junctions)

sympathetic fibers to muscle

parasympathetic fibers to muscle

sarcoplasmic reticulum

2

thin filament

actin

troponin (TnT, TnC, TnI)

tropomyosin

3

thick filament

myosin - heavy chains, 2 sets of light chains (MLC, regulatory and essential), myosin binding protein C

4

tropomyosin

2 alpha-helices that coil and reside in the grooves in the actin, serves to regulate interaction between actin and myosin

5

TnT

binds to tropomyosin

6

TnC

binds to calcium

7

TnI

binds to actin, inhibits contraction

8

MLC-1

essential, may inhibit contraction

9

MLC-2

regulatory, may enhance contraction

10

myocin binding protein C

associated with the S2 subunit of the head - may be involved in cardiomyopathies

11

titin

a giant protein that extends from the Z-line to the center of the thick filament

the portions that lie within the A-band are rigid, while the regions in the I band are more elastic

may play a role in transducing sustained stretch into a growth signal

12

Describe the conformational change of the light chain in the presence of calcium.

calcium binds to troponin C, which unblocks the active sites between actin and myosin, allowing cross-bridge cycling

13

calcium triggered calcium release

the calcium entering the cell during an action potential stimulates the release of an additional amount of calcium from the sarcoplasmic reticulum

14

From where does calcium enter the cell during an action potential?

across the sarcolemma and transverse tubules

15

What happens to calcium during relaxation of heart muscle?

removed from the cytoplasm by re-uptake of calcium into the SR by an energy dependent calcium pump

extruded from the cell to the interstitial fluid by an electrically neutral exchange for sodium

16

effect of sympathetic stimulation on the heart

increases heart rate and the slow inward calcium current

increases calcium release and increases contractility

speeds calcium reuptake process

17

Descrive the excitation-contraction coupling in cardiac muscle

1. Action potential travels along surface and down T-tubes

2. T-tube depolarization triggers SR to release Ca++ into cytoplasm of cell

3. Ca++ binds to the contractile apparatus (Troponin C)

4. Ca++ binding activates contractile apparatus and cell contracts

5. Contractile apparatus is active as long as Ca++ is remains elevated

6. The Ca++ in the cytoplasm is removed by SR Ca++ pumps and Na-Ca exchange

7. Cell relaxes as Ca++ is cleared from cytoplasm

18

cardiac glycosides

inhibit Na-K pump, which results in intracellular Na+ accumulation

19

calcium influx as a trigger for SR calcium release in cardiac muscle

1. T-tube depolarization triggers a small Ca++ influx through the DHP (dihydropyridine) receptor Ca++ channel

2. This trigger Ca++ signal binds to the SR Ca++ release channel (i.e. the ryanodine receptor).

3. Ca++ binding caused RyR to open and Ca++  is released from the SR

4. This process is called Ca++ -induced Ca++ release

20

T-type calcium channel

transient, tiny

open at more negative voltage (-50 to -60 mV)

short bursts of opening

do not interact with calcium antagonists

primarily found in atrial tissue

not affected by beta-agonists

21

L-type calcium channel

long-lasting, large

open at less negative voltage (-40 mV)

inactivate slowly

affected by calcium antagonists

found throughout the myocardium

affected by beta-agonists

22

dihydropyridine receptor (DHP)

a specialized calcium channel (L-type) in the T-tubule membrane

23

ryanodine receptor (RyR)

forms "foot" structure and is the SR calcium release channel in cardiac muscle

physically connected to the DHPR in skeletal muscle

24

calcium handling in the myocardium

75% back into the SR

25% Na-Ca exchanger

1% through sarcolemmal calcium pump and mitochondrial calcium pump

25

phospholamban

normally inhibits SR calcium pump (SERCA-2)

when phosphorylated by cAMP-dependent PKA, its ability to inhibit the SR calcium pump is lost, allowing the pump to actively pull Ca++ into the SR

26

cAMP-dependent PKA

any substance that activates this kinase will decrease inhibition of the SR Ca++ pump through phospholamban phosphorylation

agents such as epinephrine, norepinephrine, and beta-agonists do this

this accelerates Ca++ uptake into the SR, which produces myocardial relaxation

27

calsequestrin and calreticulin

proteins that bind Ca++ in the SR

in cardiac muscle, calsequestrin is dominant

both have about 50 Ca++ binding sites per protein molecule

calsequestrin and histidine-rich calcium binding protein regulate Ca++ release

28

other proteins that bind Ca++ in the SR

histidine-rich calcium binding protein and sarcalumenin

sarcalumenin regulates Ca++ pump activity

29

Describe the crossbridge cycle.

ATP binds to myosin head, cuasing dissociation of the actin-myosin complex

ATP is hydrolyzed, causing myosin heads to return to their resting conformation

a cross-bridge forms and the myosin head binds to a new position on the actin

phosphate is released and myosin heads change conformation, resulting in the power stroke and the filaments slide past each other

ADP is released, resetting the cycle

30

beta-receptor effects

activation results in the phosphorylation of phospholamban and Tn-I

increases the rate of relaxation.direct impact on ventricular filling and coronary perfusion - lusotropic effect

increases the movement of calcium into the myocardium - ionotropic effect

31

dromatropy

increases in conduction

32

chronotropy

increases in heart rate

33

ascending staircase (treppe)

with increasing frequency of contraction, there is less time for calcium to be removed from the cell

the cell accumulates calcium, resulting in more forceful contractions

causes increased number of depolarizations per minute and slower inactivation of current

34

rest potentiation

pause in repetitive contractions permits calcium stores to return to a releaseable form

contraction after the pause is augmented

35

post-extrasystolic potentiation (PESP)

premature contraction results in less calcium to release from SR

the poxt-extrasystolic beat is greater because of the increased calcium into the cells