EC Coupling I

Question 1

Sequence of events from initiation of an AP in CARDIAC MUSCLE through contraction

Answer 1

1) AP spread into t-tubule
2) During phase 2, Ca2+ enter via L-type Ca2+ channel open (DHPR) in t-membrane
3) Influx of Ca2+ triggers opening of RyR2 in SR membrane
4) Ca2+ release from SR lumen –> enter cytoplasm
5) Ca2+ bind to troponin for crossbridging and contraction

Question 2

Where is RyR2 located?

Answer 2

In the junctional SR = terminal cisternae of SR (close to T-tubule)

Question 3

Why Calcium induced calcium release?

Answer 3

Local activation of Ca2+ release so doesn’t have go far and muscle fibers can relax and contract quickly

Question 4

What is the order from greatest to least in getting rid of Ca2+

Answer 4

SERCA > NCX > PMCA to remove Ca2+

Question 5

What is SERCA2? Where is it located?

Answer 5

sarco/endoplasmic retic Ca2+ ATPase

in logitudinal SR

Question 6

What does SERCA2 do?

Answer 6

Pump out 2Ca2+ per cycle using ATP

Moves Ca2+ into terminal cisternae (SR) to be bound by calsequestrin

Question 7

Why is SERCA2 dominating the process of calcium removal? (2 reasons)

Answer 7

SERCA2 located in longitudinal SR which surrounds each myofibril

SERCA2 requires less energy b/c voltage change across SR = 0

Question 8

What balances SERCA2 pumping out Ca2+?

Answer 8

Entry of Ca2+ via L-type Ca2+ current

Question 9

What is NCX

Answer 9

Pumps 3Na+ for each Ca2+ out
Cell gains +1 charge
arrhythmogenic

Question 10

Energetics of NCX set _____

Answer 10

the reversal potential

3(ENa - Vr) = 2(ECa- Vr)
Vr = 3ENa - 2ECa

Question 11

What is PMCA? What does it do?

Answer 11

plasma membrane calcium ATPase
pump 1 Ca2+ ion per cycle
moves Ca2+ out of cell

Question 12

Difference in EC Coupling between Skeletal and Cardiac muscle (calcium entry)

Answer 12

Cardiac=
1) requires entry of external Ca2+

Skeletal =
1) does not require entry of external CA2+

Question 13

Difference in EC Coupling between Skeletal and Cardiac muscle (Structure of DHPR)

Answer 13

Cardiac =
1) CaV1.2

Skeletal =
1) CaV1.1

Question 14

Difference in EC Coupling between Skeletal and Cardiac muscle (How Ca2+ released from SR)

Answer 14

Cardiac =
1) via RyR2

Skeletal =
1) via RyR1

Question 15

How is EC coupling the same between Skeletal and Cardiac muscle

Answer 15

Ca2+ binds to trop on thin filaments and activates contraction

Question 16

How does NCX govern direction of Ca2+ and Na+ movements

Answer 16

1) If depolarized to 0 mV, Ca2+ enters via NCX until [Ca2+]i = 2 um

2) As [Ca2+]i > 2 um, Ca2+ exits via NCX
3) Upon repol to -74 mV, Ca2+ keeps exiting until [Ca2+]i = 100 nM

Question 17

What is the default direction of ion flow via NCX?

Answer 17

Na exit

Ca 2ntry

Question 18

What is the direction of ion flow in NCX if Ca2+ is released from SR?

Answer 18

Na influx –> depolarization

NCX depolarization by diastolic SR calcium release –> pacemaking of SA node

Question 19

Depolarization via NCX due to abnormal diastolic SR Ca2+ release is ____

Answer 19

a trigger for delayed after depolarizations that lead to arrhythmias

Question 20

How is calcium homeostasis maintained in short term

Answer 20

if calcium influx > efflux, calcium storage in SR increased

if calcium influx < efflux, calcium storage in SR decreased

Question 21

What are 2 exchangers important for calcium homeostasis?

Answer 21

1) NCX calcium exchanger

2) L-type calcium channel

Question 22

How does L-type ca channel maintain homeostasis

Answer 22

via Calcium-dependent inactivation

Depends on Ca2+ entering L-type and Ca2+ released via RyR2

Question 23

If amount of CA2+ in SR increases (and amount released via RyR2 ____), then greater CDI causes ____ Ca2+ to enter via the L-type channel

Answer 23

If amount of CA2+ in SR increases (and amount released via RyR2 increases) then greater CDI causes less Ca2+ to enter via the L-type channel