Excitation/Contraction Coupling Flashcards
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
thin filament
actin
troponin (TnT, TnC, TnI)
tropomyosin
thick filament
myosin - heavy chains, 2 sets of light chains (MLC, regulatory and essential), myosin binding protein C
tropomyosin
2 alpha-helices that coil and reside in the grooves in the actin, serves to regulate interaction between actin and myosin
TnT
binds to tropomyosin
TnC
binds to calcium
TnI
binds to actin, inhibits contraction
MLC-1
essential, may inhibit contraction
MLC-2
regulatory, may enhance contraction
myocin binding protein C
associated with the S2 subunit of the head - may be involved in cardiomyopathies
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
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
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
From where does calcium enter the cell during an action potential?
across the sarcolemma and transverse tubules
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
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
Descrive the excitation-contraction coupling in cardiac muscle
- Action potential travels along surface and down T-tubes
- T-tube depolarization triggers SR to release Ca++ into cytoplasm of cell
- Ca++ binds to the contractile apparatus (Troponin C)
- Ca++ binding activates contractile apparatus and cell contracts
- Contractile apparatus is active as long as Ca++ is remains elevated
- The Ca++ in the cytoplasm is removed by SR Ca++ pumps and Na-Ca exchange
- Cell relaxes as Ca++ is cleared from cytoplasm
cardiac glycosides
inhibit Na-K pump, which results in intracellular Na+ accumulation
calcium influx as a trigger for SR calcium release in cardiac muscle
- T-tube depolarization triggers a small Ca++ influx through the DHP (dihydropyridine) receptor Ca++ channel
- This trigger Ca++ signal binds to the SR Ca++ release channel (i.e. the ryanodine receptor).
- Ca++ binding caused RyR to open and Ca++ is released from the SR
- This process is called Ca++ -induced Ca++ release
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
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
dihydropyridine receptor (DHP)
a specialized calcium channel (L-type) in the T-tubule membrane
ryanodine receptor (RyR)
forms “foot” structure and is the SR calcium release channel in cardiac muscle
physically connected to the DHPR in skeletal muscle
calcium handling in the myocardium
75% back into the SR
25% Na-Ca exchanger
1% through sarcolemmal calcium pump and mitochondrial calcium pump
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
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
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
other proteins that bind Ca++ in the SR
histidine-rich calcium binding protein and sarcalumenin
sarcalumenin regulates Ca++ pump activity
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
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
dromatropy
increases in conduction
chronotropy
increases in heart rate
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
rest potentiation
pause in repetitive contractions permits calcium stores to return to a releaseable form
contraction after the pause is augmented
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
