how does heart work 2

Question 1

Length dependency of a muscle:

Answer 1

1. the longer the muscle is: the more force it generates.
2. In isolated muscle fibers and also in the heart.
3. This is called the preload dependency.

Question 2

Integrated cardiac performance:

Answer 2

1. pressure volume loop.

2. When cardiac muscle LV increases volume, the amount of blood ejected increases

Question 3

PKA functions to

Answer 3

1. phosphorylate TnI and influences actin and myosin relationship to allow for more actin and myosin interactions can take place ,
2. also increase the amount of Ca influx from the Ca2+ channel
3. PKA inhibits PLB, which inhibits SERCA, to allow for CA2+ to cycle out of the SR more rapidly.

Question 4

B adrenergic signal causes

Answer 4

an increase in extracellular ca2+ AND intracellular Ca2+

Question 5

Major coordinate responses of hear muscle to beta adrenergic stimulation:

Answer 5

phosphorylation of:

1. Ca channels (SAN cells)
2. Ca channels (ventricular cells)
3. Na pump
4. phospholamban
5. FKB
6. troponin I

Question 6

phosphorylation of Ca channels (SAN cells) will result in

Answer 6

1. ↑ Heart rate
2. Improved CO
   (CO=HR x SV)

Question 7

Phosphorylation of Ca channels

(ventricular cells) will result in

Answer 7

1. ↑ Ca entry
2. ↑ Force of contraction
3. improved EF (+ inotropy)

Question 8

Phosphorylation of Na pump

will result in

Answer 8

1. ↑ Ca efflux (via Na-Ca exchange)

2. Enhanced relaxation and diastolic filling

Question 9

Phosphorylation of Phospholamban will result in

Answer 9

1. Disinhibition of SR calcium pump (SERCA2)
2. Increased SR calcium load
3. improved diastolic filling

Question 10

Phosphorylation of FKB

will result in

Answer 10

1. Enhances Ryr receptor mediated calcium release

2. enhanced contractility

Question 11

Phosphorylation of troponin I

will result in

Answer 11

1. ↓ Ca affinity for TnC

2. enhanced relaxation

Question 12

bigger hearts result in

Answer 12

bigger contractions

Question 13

SV is a measure of

Answer 13

end diastolic volume

because of the length/tension relationship

Question 14

short contractions (muscle shorter) means the interactions between myosin and actin are

Answer 14

less

Question 15

big contractions (muscle longer) means the interactions between myosin and actin are

Answer 15

greater

Question 16

muscle can increase force of contraction by

Answer 16

1. getting longer

2. if exposed to inotrope and shift Frank starling curve

Question 17

myosin alpha vs beta

Answer 17

α myosin has greater ATPase activity than β

this means that α has more activity, so it would be more prevalent in a mouse, whose heart beats 400 times a minute (all alpha) , than in an elephant whose is more like 40 and would have all β

Question 18

ATPase is proprtional to

Answer 18

resting HR per minute

Question 19

how does LV hypertrophy lead to Chronic HF?

Answer 19

1. heart develops LVH, decrease CO because heart is ejecting against an increased afterload
2. heart falls apart, the frank starling curve shifts down
3. volume increases and the ability to eject decreases

Question 20

LVH : Cellular mechanisms

Answer 20

1. Likely increase in Ca current via
   L-type Ca channel
2. Reduced SR pump fxn
   (↑ PLB/SERCA2 ratio)
3. Impaired myofilament relaxation
4. Altered (increased) cytosolic calcium and new steady-state
5. post transcriptional and post translational modifications

Question 21

LVH: Early/acute modification:

Answer 21

1. PKA

2. PKCβ

Question 22

LVH: Late/Chronic modification:

Answer 22

1. PKCε / PKD
2. CAMκ
3. calcineurin

Question 23

triggers for LVH are

Answer 23

1. neurohormonal modulators
2. genetic factors
3. exercise
4. stretch
5. hypertension

Question 24

Hypertrophic remodeling results in

Answer 24

1. ↑βMHC
2. ↑ ANF
3. ↓ αMHC
4. ↓ SERCA2

Question 25

Hypertrophic heart is not only different in the appearance, but it also

Answer 25

handles calcium differently and signals differently

Question 26

Calceneurin

Answer 26

1. is activated by calcium 2. It is a phosphatase. 3. It takes a super long time (hours) for it to be activated. 4. When it becomes activated,it dephosphorylates Nfat and nfat is activated and it goes into the nucleus.

Question 27

how can you make a mouse have dilated cardiomyopathy?

Answer 27

1. dephosphorylate NFAT or 2. chronically activate calceneurin, 3. they contract poorly and have txn factors like human with dilated cardiomyopathy

Question 28

______ is one of the key markers in dilated cardiomyopathy

Answer 28

Increase in cytosolic calcium

Question 29

Adaptations to a chronic load is

Answer 29

complex, coordinated and involved changes at the txn level which cause the heart to be reconfigured.

Question 30

How do you measure heart function?

Answer 30

using ejection

Question 31

progressive decline in cardiac function after a heart attack results from

Answer 31

a series of positive feedback loops it takes a big hit. Progressive cardiac dysfunction from the lack of positive feedbacks