cardiac contraction

Question 1

duration of AP

Answer 1

200-500ms

Question 2

what is the force of contraction proportional to

Answer 2

[Ca2+]i

Question 3

[Ca2+]i during systole

Answer 3

~1uM

Question 4

[Ca2+]i at maximum contraction

Answer 4

~10uM

Question 5

why doesn’t [Ca2+]i usually reach 10uM

Answer 5

Normally cell shortening is submaximal

Question 6

what happens in the depolarisation phase

Answer 6

ca signal and cell shortening - when Ica is generated

Question 7

what happens in the repolarisation phase

Answer 7

cell relaxation - when ca2+ signal is reduced.

Question 8

what is contraction determined by

Answer 8

INCREASE in IC Ca2+ levels

Question 9

what does a higher increase in [Ca2+]i lead to

Answer 9

increased force of contraction

Question 10

how does [Ca2+]i change

Answer 10

from 0.1uM to about 10uM

Question 11

which receptor does calcium active on the sarcoplasmic reticulum

Answer 11

Ryanodine / calcium induced calcium release (CICR)

Question 12

what causes Ca release from SR

Answer 12

(AP upstroke) Na+ ions depolarise T tubules, activating VDCCs, allowing Ca2+ influx
Ca binds to RyR /CICR on SR - close association with T tubules
Release of Ca from SR

Question 13

How does rise in [Ca2+]i cause myosin-actin interactions

Answer 13

Originally my-ac binding sites blocked by troponin-tropomyosin complex;
ca2+ displaced troponin-tropomyosin;
binding sites exposed, cross bridge formed;
myosin head flexes to move actin and Z line to sarcomere centre: contraction

Question 14

what is troponin made up of

Answer 14

TnT - binds to tropomysoin
TnI - binds to actin to hold tropomyosin in place
TnC - binds Ca

Question 15

how does tropomysoin get displaced

Answer 15

binding of Ca to TnC subunit, exposing actin binding sites

Question 16

Other clinical significance of TnI and TnT

Answer 16

important plasma markers for cardiac cell death

Question 17

how does decrease in [Ca2+]i occur

Answer 17

(AP downstroke) K+ ions repolarise T tubules - VDCCs close, decrease in Ca influx;
no Ca influx, no CICR; extrusion of Ca from cell (30%) by Na/Ca exchanger

Question 18

Where does Ca uptake occur in decreased [Ca2+]i

Answer 18

into SR via SR Ca2+ATPase (SERCA, 70%) - Ca in SR for next contraction;
uptake of Ca in mitochondria

Question 19

fancy name for contractility

Answer 19

inotropy

Question 20

drugs used to correct acute or chronic heart failure do what to the heart

Answer 20

increase its contractility

Question 21

how do drugs increase contractility

Answer 21

increase [Ca2+]i levels

Question 22

how do heart failure drugs increase contractility/[Ca2+]i levels

Answer 22

increase VDCC activity OR

reduce Ca2+ extrusion

Question 23

what classes of drug increase VDCC activity

Answer 23

sympathetic mimetic

Question 24

what classes of drug reduce Ca2+ extrusion

Answer 24

cardiac glycosidases

Question 25

how does beta 1 adrenoceptor stimulation a contractility increase

Answer 25

``` NA binds B1 > Gs, AC, inc cAMP inc PKA, inc Pi'n of VDCCs inc Ca influx, inc CICR inc sliding filament mechanism inc contractility ```

Question 26

effect of increased PKA on force of contraction

Answer 26

increased Ca2+ influx | increased FOC

Question 27

effect of increased PKA

Answer 27

``` increased open K channels increased repolarisation inc SERCA activity increased Ca uptake both increase relaxation ```

Question 28

sympathetic effect on inotropy

Answer 28

positive - increased contractility

Question 29

sympathetic effect on chrontropy

Answer 29

positive - increased HR

Question 30

Sympathetic effect on dromotropy

Answer 30

positive - increased conduction through AV node

Question 31

sympathetic effect on relaxation

Answer 31

positive lusitropic effect - increase rate of relaxation, K channels, SERCA

Question 32

what are drugs that have positive inotropic action called

Answer 32

inotropes

Question 33

examples of inotropes

Answer 33

cardiac glyocsidases

Question 34

how does digoxin work

Answer 34

reducing Ca2+ extrusion

Question 35

what does digoxin do

Answer 35

increase contractility

Question 36

what is the mechanism of action for digoxin

Answer 36

inhibits Na+/K+ ATPase causing [Na+]i build up less Ca2+ extrusion by NCX More Ca uptake by stores, therefore greater CICR

Question 37

what do dobutamine and dopamine act on

Answer 37

beta one adrenoceptors - may be used in acute heart failure

Question 38

where does glucagon act

Answer 38

acts on Gs coupled receptor - increase cAMP and PKA activity - used in patients with acute heart failure that take B blockers

Question 39

what is amrinone

Answer 39

a phosphodiesterase inhibitor (PDE)

Question 40

which PDE is heart specific

Answer 40

Type 3/PDE3

Question 41

how does PDE reduce cAMP

Answer 41

by converting cAMP to AMP

Question 42

what is the result of PDE's conversion of cAMP to AMP

Answer 42

reduction in cAMP, reduced activity of PKA

Question 43

what is the IC result of PDE inhibition

Answer 43

cAMP build up - PKA activated to increase activity of VDCCs and increased Ca2+ - only used in transplant cases

Question 44

what is the link between electrical activity, change in [Ca2+]i, and contraction

Answer 44

higher activation of VDCCs higher Ca2+ influx stronger force of contraction

Question 45

what causes a rise and a reduction in [Ca2+]i in cardiac myocytes

Answer 45

u

Question 46

what is the importance of a submaximal effect of [Ca2+]i in cardiac myocytes - how does this differ to skeletal muscle?

Answer 46

n

Question 47

how does a rise in [Ca2+]i produce contraction?

Answer 47

fin

Question 48

can you define the differences between inotropy and Starling's law

Answer 48

i

Question 49

Can you describe the effects of the SNS on the heart?

Answer 49

sh

Question 50

?

Answer 50

ed