Cardiac Muscle Mechanics Flashcards
1
Q
Cardiac muscle appearance
A
- striated and contains gap junctions
- has large intercalated discs that separate adjacent myocytes communicate with gap junctions
- T-tubules exist and invaginate the X-lines
- uni- or binucleate but all are mechanically and electrically connected to one another, the entire tissue resembles a single, giant muscle cell
- cardiac muscle is functional syncytium
- Ca from outside the cell and calcium release from SR and contraction of sarcometers
- aerobic metabolism
- has mitochondira and myoglobin
- energy reserves with glycogen and lipid inclusions
2
Q
T-tubule in cardiomyocyte
A
- T tubules only occur at Z lines
- ryanodine receptor opened by calcium induced calcium release (CICR)
- small amount of Calcium influex in L type calcium channel binds to Ryandodine receptor in SR and causes the Ryanodine receptor to open then the ryanodine receptor allows large amounts of calcium to flow out of the SR lumen into the sarcoplasm, leading to muscle contraction
3
Q
Cardiac AP
A
-Phase 0- Depolarization- Rapid Na channels are stimulated to open, positive change in transmembrane potential
-Phase 1- initial state of repolarization triggered by closing of Na+ channels and the brief actibation of Ito the transient outward current
-Phase 2- plateau because of rate of repolarization slowed by influx of Ca2+ ions slowly, expends refractory period
-Phase 3- later stages of repolarization, K+ current out
Phase 4- after repolarization complete
- cardiac AP 250 msc (skeletal 5msec), this prevents summation heart only contracts by twitch
- cardiac AP is calcium dependent, skeletal AP is Na dependent and does not allow much calcium entry
4
Q
AP propagation in cardiomycocytes
A
- cardiac AP propagate through gap junctions between cells
- depolarization in one cell increases positive charge within that cell and that causes displacement of positive charges through gap junction and depolarization of the next cell
5
Q
Calcium in contraction
A
- during depolarization (phase 2) calcium enters sarcoplasm via L type Ca channels (20% external calcium)
- calcium entry into sarcoplasm triggers Ryanodine receptor ( they are in sarcoplasmic reticulum membrane) opening in CICR from SR (80% calcium elevation)
- neighbors open triggering domino effect
- during depolarized phase the sodium calcium exchanger can work in reverse and exchange 1 calcium ion into the cell for every 3 sodium out (minor)
6
Q
Calcium during relaxation
A
- L type calcium channels inactivate and cells begin to repolarize, there are different calcium clearance
- sarcoplasmic and endoplasmic reticulum ATPase (SERCA) uses the energy of ATP hydrolysis to pump calcium ions back into the sarcoplasmic reticulum (80%)
- Sodium calcium exchange (NCX) resumes normal operation and expels 1 calcium for every 3 sodium ions let in (15% of calcium removed)
- 5% removed by plasma membrane calcium ATPase (PMCA) pumps calcium out of cell
- mitochondiral calcium uniporter removes small amount of sarcoplasmic calcium
- HEART IS MORE SENSITIE TO L-type CALCIUM CHANNEL BLOCKERS (than skeletal)
7
Q
TroponinC and Tropomyosin in Cardiac Muscle
A
- works like skeletal muscle in that calcium binds TroponinC which leads to movement of Tropomyosin off the myosin binding sites on the thin filament
- this allows myosin head to bind to the thin filament and initiates the crossbridge cycle
- cardiac contractions are twitches, there is no summation and the twitch is terminated by calcium clearance
- cardiac muscle expresses specific forms of myosin heavy chain that are different from skeletal muscle
8
Q
Relationship of AP, calcium and tension in a cardiac twitch
A
- AP-about 250 msec, plateau to prolong duration. Long refractory period, respond only to twitches. Muscle fibers are electrically coupled in two functional syncytia-the atrial and ventricular syncytium
- no recruitment
- tension- similar to skeletal, can be affected if sarcoplasmic Ca altered by inotropic agent or if the calcium sensitivity of myofilaments is altered (by changing initial length)
- cardiac muscle- SA node is spontaneously active and triggers an endogenous heart rate of 100 bpm, normally reduced under parasympathetic vagal nerve (ACh release) to about 60 bpm
9
Q
Length tension relation in cardiac muscle
A
- effect of an increase in initial length of cardiac muscle
- the amount of Ca released by SR does not change but developed tension increases- FRANK STARLING law of heart
- states that the more the ventricle is filled with blood during diastole, the greater the volume of ejected blood will be during the resulting systolic contraction
- does not change amount of overlap
- increased load stretches the myocardium and increases the affinity of troponin C for calcium, leading to an increase in contractile force for a given level of sarcoplasmic calcium (sensitivity)
- human heart, maximal force is generated with initial sarcomere length of 2.2 micrometers
10
Q
effects of greater initial length on cardiac muscle function
A
- Increased Po, same Vmax
- the velocity of shortening increases
- the amount of shortening increases
- the work of the heart increases
- the power delivered by the heart increases
11
Q
Length tension relationship and Frank Starling Law
A
- it is shifted in relation to the skeletal curve and the force increases over the SL range where myofilament are overlapped- mechanisms other than overlap play an important role in cardiac muscle tension
- difference underlies Frank Starling Law
- now believe that TroponinC’s affinity for calcium ions increases as the sarcomere is stretched
- the greater the ventricular filling during diastole, the greater the stretch of the sarcomere, the greater TnCs affinity for calcium, the more crossbridge formation per AP, and the greater the force of systolic contraction
12
Q
Inotropic agents in cardiac twitch
A
- inotrophic intervention (norepi)
- the amount of Ca released by the SR increases, thus increasing the force of contraction
- increase in contractility
- inotropic agents increase the force of contraction, or contractility, by increasing the amount of calcium released from the SR
- NE + B1 adrenergic receptor -> increase cAMP -> increase PKA -> increase calcium -> increase tension
- AP changes immediately following NE addition (increased influx of Ca_ but increase in contractility takes 8 beats to reach
- increase the strength of contraction, and increase the rate of rise of tension but shorten the duration of contraction (shorten duration of systole allows more time for diastolic filling- useful in exercise)
- B-adrengeric stimulation is positive inotropic and positive chronotropic (increase heart rate)
13
Q
Calcium tension curve with sensitivity and contractility changes
A
- a sensitivity change increase shifts the curve up, more tension is produced at same calcium level (increase sensitivity change by increasing initial length
- a contractility increase shifts the muscle response along the calcium tension curve. More tension is produced because of more calcium per AP, increase Ca influx (norepi). This also shifts the length tension up
- Maximal load increases at all lengths
