L4 Flashcards
what is the contractile unit of a muscle cell
the sarcomere
do the peaks on the ECG happen before or after the contraction in the heart
before
what kind of event is an excitation contraction coupling
electro mechanical as electrical and mechanical activity overlap in time
what are the major components of excitation contraction coupling
Ca2+ entry
contraction (the contractile machinery)
getting the Ca out of the cells
what causes Ca entry
the cell membrane depolarises causing the membrane potential to rise
when this reaches the threshold for L type Ca channels they open and Ca enters the cell
the influx of Ca into the cell binds to the ryanodine receptor Ca2+ releasing channels (RYR2) which triggers the release of Ca form the SR
why do you get Ca2+ induced Ca2+ release
the density of RYR2 is very high near LTCC and the distance between them is very small (10 -20nm)
where does most of the Ca come from for the contraction
what channels does it come through
about 75% comes from the SR with only 25% coming from the extracellular environment through the LTCC
this difference is even larger agon in smaller mammals
in cardiac muscle, depolerisation causes….
A) direct opening of Ca2+ release channels (RYR2) on the SR
B) Ca induced Ca release
C) increased intracellular CA from 1 mM to 10 mM
D) opens funny Na channels
B
what is the extracellular concentration of Ca
2 mM
what is the intracellular concentration of Ca
0.001 mM
what is the concentration of Ca in the cytosol
0.1 - 1 uM
what causes contraction
Ca binds to troponin C
tropomyosin moves and acting and myosin interact
what are the 3 parts of the troponin complex
TnC = Ca binding domain
TnI = inhibitory domain
TnT = tropomyosin binding domain
what sequence causes the sarcomere to shorten
Actin binding sites are blocked until Ca2+ binds to TnC which causes the displacement of Troponin-Tropomysin
Interaction Actin-Myosin = cross-bridge
Myosin heads flips – ratchet action
Actin moves toward center
of sarcomere
Sarcomere shortens
Actin and Myosin don’t
describe the cross bridge cycle
ATP bound to Myosin split in ADP and Pi
Myosin has high actin affinity
Ca2+ increases, binds to
TnC, opens binding
place, Myosin moves to
Actin and binds
Energy released (ADP + Pi)
and Myosin head shifts from
90 to 45 degrees. this is the powerstroke
Ca2+ decreases, ATP binds,
Myosin has low actin affinity,
cross-bridge detaches
what is the sliding filament theory
Myosin is pulling actin towards center of the sarcomere.
Actin filaments slide along adjacent myosin filaments by cycling of cross-bridges with myosin
Z lines come closer together and cell shortens thus
producing force or tension
how many myosin heads are there on a myofilament
600
what increases the strength of contraction of the heart
what rest what % of cross bridges are formed
Contraction more forceful due to increase in the number of cross-bridges, and not due to more contracting cardiomyocytes
normally cross bridge cycling happens at about 20-40% meaning that it is possible to recruit more myofilament
During contraction of the sarcomere:
A. Myosin is pulling actin towards the center of the sarcomere
B. Myosin shortens moving actin towards the center of the sarcomere
C. Actin shortens causing the z-lines to move towards the center of the sarcomere
D. Both actin and myosin shorten
A
what is relaxation
it is the end of the contraction as Ca influx ceases
the SR is no longer stimulated to release Ca
and the cytosolic Ca must be rapidly reduced
what are the 3 different mechanisms to reduce intracellular Ca
SERCA
Na/Ca exchanger
Ca ATPase
describe how the SERCA pump decreases intracellular Ca levels
SERCA is ATP-dependent and pumps cytoplasmic Ca2+ back into SR (75% which is what the SR released to keep it balanced)
SERCA activity is regulated by Phospholamban (PLB),
PLB protein phosphorylation stimulates Ca2+ uptake as it removes the inhibition on the SERCA pump
describe how the Na/Ca exchanger (NCX) pump decreases intracellular Ca levels
Na+ / Ca2+ exchange pump, driven by Na+ gradient (cotransport = secondary transporter)
this is responsible for getting rid of 24% of the intracellular Ca levels
describe how the Ca ATPase pump decreases intracellular Ca levels
PMCA - plasma membrane Ca atpase
it is located in the membrane and uses ATP to pump Ca out of the cell
this is what gets the remaining 1% of Ca out of the cell
what makes cardiomyocytes inexitable
2 reasons
“Stable” Ca2+ plateau makes cardiomyocytes inexcitable
they also have long absolute (250ms) and relative refractory periods (300ms) which prevents re-excitation during most of contraction period. it also prevents circuitous recycling of APs
how long is the absolute refractory period in a cardiomyocyte
250ms
how long is the relative refractory period in a cardiomyocyte
300ms
why do cardiomyocytes need to have long periods of time where that are inexcitable
It has a long refectory phase because it needs to be relaxed so that the heart can be filled with blood again then it wouldn’t function (it would be in tetanus and you would die)
Therefore in the heart summation is not possible because the heart has to completely relax
how much ATP does the heart make in a day
3.5 - 5 kg per day
what kind of metabolism does the heart use
aerobic metabolism (oxidation)
what % of the hearts energy comes from oxidising fatty acids
60 - 75%
what % of the hearts energy comes from oxidising glucose
25 - 40%
what suplys O2 to the heart
coronary circulation
at the heart O2 extraction from the blood is very high. what % of O2 is extracted
75%
the heart is very vulnerable to coronary ear disease/ischemia, why is this
When you look at these vessels they have a feather like appearance over the heart as there is a capillary for almost every cardiomyocyte
The down side of this process is that the hearts is very vulnerable to decreased blood flow
During a heart attack you get a blockage in one of more of these vessels which stops the blood flow which stops the oxygen. This is called ischemia
