Cardiac Muscle

Question 1

cardiac muscle

Answer 1

• striated and has A and I bands
• intercalated discs separate adjacent myocytes
• boundaries apposed and bound by gap junctions and desmosomes
• structurally stabilize cells and allow direct electrical connection between the cells
• T tubules invaginate at Z line
• multinucleate but not as many as skeletal
• branched
• functional syncytium
• AP triggers calcium influx from outside cell and SR and causes contraction of the sarcomeres
• dependent on aerobic metabolism
• sarcoplasm has large numbers of mitochondria

Question 2

cardiomyocyte T tubule

Answer 2

• only occurs at Z lines, not whole muscle fiber
• doesn’t have 2 endfeet
• ryanodine receptor opened by CICR
• small influx thru L type channels, Ca binds to ryanodine receptors in SR and opens them

Question 3

cardiac action potential-ventricle

Answer 3

• sustained period of calcium entry
• phase 0 Na current
• Phase 1 transient outward current
• Phase 2 Ca in K out
• Phase 3 K out
• Phase 4 rest
• 250 msec
• length of AP and refractory period prevent summation, heart contracts only by twitch

Question 4

AP propagation in cardiomyocytes

Answer 4

• propagate through gap junctions
• depolarization in once cell increases positive charge within that cell and causes displacement of pos charges into next cell via gap junction
• causes depolarization of the next cell

Question 5

calcium elevation during excitation

Answer 5

• AP causes influx of Ca through L type channels- contributes 20% of Ca elevation and twitch
• This calcium triggers the ryanodine receptors on SR via CICR- contributes the other 80%
• can trigger neighboring ryanodine receptors
• in low calcium binds to high affinity stop and opens receptors but if a lot of calcium, high affinity site closes receptor
• NCX (Na/Ca exchanger) works in reverse and pumps Na out and Ca in

Question 6

calcium clearance during relaxation

Answer 6

• L type channels inactivate and cell repolarizes
• SERCA-ATPase pumps Ca back into SR- 80%
• NCX resumes normal operation- 3 Na in 1 Ca out (15%)
• 5% removed by plasma membrane ATPase (PMCA) out of cell
• mitochondrial calcium uniporter removes small amount of sarcoplasmic calcium
• heart is more sensitive to L type channel blockers

Question 7

cross bridge cycle

Answer 7

• same as skeletal
• Ca binds Troponin C which moves Tropomyosin off myosin binding sites on actin filament
• no summation
• terminated by calcium clearance

Question 8

temporal relation

Answer 8

• AP 200 ms, then ICa then contraction
• AP duration and refractory period long with respect to tension development-no summation
• plateau on AP prolongs contraction and has a long refractory period
• no recruitment
• tension can be affected by changes in calcium concentration (inotropic agent) or sensitivity to calcium (changing initial length)

Question 9

length tension and starling law

Answer 9

• tension generation is sensitive to initial length even when there is maximal overlap between thick and thin filaments
• calcium amount doesn’t change that much
• will pump no matter what blood is there
• more blood is more initial length and can generate more tension- goes along with increasing end diastolic volume increases stroke volume/force of contraction
• occurs because increasing length increases affinity of troponin C for calcium-increase in senstivity
• maximum at 2.2 micrometers

Question 10

effects of greater initial length

Answer 10

• increased Po
• increased shortening
• increased work
• increased power

Question 11

cardiac length tension vs skeletal

Answer 11

• despite maximum overlap, still increases in tension, would expect flat line like skeletal- optimal overlap means max tension
• increases in length cause increase in Ca affinity from troponin C-can still generate more tension- increased sensitivity
• in skeletal muscle- too small is steric hindrance, too big is no overlap

Question 12

inotropic agents can also increase tension

Answer 12

• norepi and b1 receptor- Gs- increases cAMP, PKA, which increases calcium and therefore tension
• significant increase in calcium-increase in contractility (tension)
• norepi increases AP amp and duration several beats before an increase in tension is detected (8 beats)-need Ca to catch up with increase in AP

Question 13

norepi

Answer 13

• shortens twitch duration by accelerating SR reuptake and removal from sarcoplasm
• increases strength
• increases rate of rise of tension
• shortens duration of contraction
• shortened systole allows more time for filling (increased contractility from norepi associated with increased HR)

Question 14

norepi 2

Answer 14

• increased cAMP increases amount of Ca influx and therefore CICR
• also activates PKA and activates phospholamban-increased sensitivity of SR Ca pump- can get it back faster to let it out again
• increased strength and decreases duration

Question 15

calcium tension curve

Answer 15

• shows sensitivity increase by shifting the curve up-Ca stays about the same, tension still increases (initial length was longer)
• contractility increase shifts curve to right because it actually increases the amount of calcium

Question 16

length tension curve

Answer 16

• changes in contractility shift curve up
• still starts at 13 mm, more tension generated (more Ca)-more isometric tension
• contracts more when after load is added- 11 mm vs 12mm from control