Preload, Afterload & Contractability

Question 1

What is the cardiac myocyte basic unit of contractions?

Answer 1

1) contractile cells
2) nodal cells
3) purkinje fibers

Question 2

How is contraction elaborated and what is the key player in this process?

Answer 2

Elaborated via the conduction system in response to an AP the delivers Ca to contractile proteins
-Calcium is the key player

Question 3

What does contractile force depend on?

Answer 3

Ca

Question 4

How does calcium react to the wave of depolarization from the AP?

Answer 4

• increase Ca concentration follows wave of depoarization

- Ca moves down steep conc gradient from outside to inside cell during propagating AP

Question 5

What are T-tubules?

Answer 5

• are extensions of sarcolemma (PM) that convey excitement deep into the interior of the cell
• allows deep muscles to contract
• associated with Sarcoplasmic reticulum

Question 6

What is the sarcoplasmic reticulum?

Answer 6

• Ca storage site
• form an intricate web of intracellular tubules that cover the sarcomeres
• closley associated with T-tubules

Question 7

what is SERCA?

Answer 7

• pumps that cover the sarcoplasmic reticulum

- suck Ca from cytoplasm back into SR during diastole (relaxation)

Question 8

what is Calcium Induced Calcium Release?

Answer 8

• AP causes T-tubule depolarization, opens L-type Ca channels, small amount of external Ca enters
• causes major internal Ca release by binding to Ca release channels (ryanodine receptors) on the SR
• Ca binds and activates contraction
• then re-uptaken by Serca, #Na/Ca exchanger, and Ca PM pumps
• low Ca levels allows relaxation

Question 9

Where does Ca for contraction come from? Why?

Answer 9

• 15% extracellular , 86% from intracellular SR storage

- diffusion of Ca from external–> internal takes too long

Question 10

why use T-tubule and SR system?

Answer 10

-ensures uniform and synchronous delivery of internally stored Ca to DEEP muscle fibers

Question 11

what are the 4 ways Ca is mobilized (2) & re-sequestered (x2)from cytoplasm ?

Answer 11

1) SERCA (main)
2) 3Na/Ca exchanger
3) L-type Ca channels
4) Ryanodine Receptor (Ca release channels)

Question 12

what determines force of contraction?

Answer 12

-the amount of Ca and rate of arrival at myofilament

Question 13

How does Ca alter the force of contraction?

Answer 13

-more Ca causes removal of more troponin from tropomyosin, allows more myosin cross bridge to bind and a greater contractile force as a result

Question 14

How does skeletal muscle react to Ca release?

Answer 14

-skeletal muscle reacts maximally due to large Ca concentrations fully saturating myofilaments

Question 15

How does cardiac muscle react to Ca release? what does this indicate?

Answer 15

• activates sub maximally
• under normal conditions AP results in only 50% of max contraction
• means force of cardiac muscle contraction is regulated by amount of Ca release due to AP

Question 16

Can heart AP be summated?

Answer 16

-no, the cardiac myocytes are electrically coupled, when 1 myocyte activated all are activated

Question 17

factors promoting large Ca release?

Answer 17

• norepinephrine
• epinephrine
• caffeine
• elevated serum Ca

Question 18

factors that promote less Ca release

Answer 18

1) barbiturates
2) beta-blockers
3) hypoxia

Question 19

How does T-tubule depolarization trigger SR Ca releasE?

Answer 19

1) T tubules and SR membrane have Didactic Cleft between them, when T tubule depolarized L type Ca channels release Ca into cleft
2) this activator Ca is the Ca+ spark indicated increase local Ca conc, causes Ryanodine Receptor to open, release Ca into cytoplasm(CICR)

Question 20

How Ca re-sequestered and removed to allow relaxation?

Answer 20

1) SERCA is main determinant, regulating by inhibitor protein
2) 3Na/CA exchanger is next in line, (3Na in down gradient for 1 Ca out)
3) PM Ca Pump, very low yield

Question 21

Amount of Ca in SR?

Answer 21

• is constant beat to beat so what is released must be re-sequestered
• amount fo Ca in SR effects contraction force

Question 22

How are contractile force and relaxation interrelated?

Answer 22

• SERCA pumps 70-90% of released Ca back into SR so is major determinate of relaxation rate
• increased search enhances relaxation, greater SR filling and more Ca available for next beat