EC Coupling and Calcium I

Question 1

What is the DHPR and where is it located?

Answer 1

The DHPR is the dihydropyridine receptor and is the voltage gated Calcium channel located in the plasma membrane

Question 2

What is the RyR receptor and where is it located?

Answer 2

It’s the Ryanodine receptor, located on the terminal cisternae of the SR (sarcoplasmic reticulum). It’s a calcium channel.

Question 3

T or F?

The ryanodine receptor in cardiac muscle is the same as that of skeletal muscle?

Answer 3

False.

It’s RyR2 in cardiac muscle, RyR1 in skeletal muscle.

Question 4

T or F?

The ECC in carciac muscle does NOT require the entry of external Calcium.

Answer 4

False

The ECC does in fact require external calcium to enter.

Question 5

What type of calcium channles exist in the t-tubules?

Answer 5

The gates in the t-tubules are voltage gated L-type calcium channels which open upon depolarization of the t-tubule.

Question 6

How is the ECC sequence initiated in cardiac muscle?

Answer 6

Calcium enters the cardiac muscle cells via the DHPR and activates the RyR2, which in turn causes a large flux of calcium release from the SR

Question 7

Once calcium has entered the cell (via DHPR) and activated the RyR2 receptor causing a flux of calcium from the SR into the cell, what is the next step?

Answer 7

The calcium then binds to troponin on the thin filaments, exposing the myosin binding site and allowing for contraction of the cardiac muscle.

Question 8

In order to initiation the ECC, what has to happen/spread throughout the cardiac muscle cell? What does this do to lead to contraction?

Answer 8

An action potential has to spread through the T-tubules. It’s this action potential that opens the DHPR gates and allows for extracellular calcium to enter into the cell.

Question 9

It’s now time for the cardiac muscle to relax. How is this accomplished (2 different ways), and which is more important?

Answer 9

1) SERCA2 pump in then SR pumps calcium back into the SR (2 Calcium ions per cycle)
2) The NCX Na⁺/Ca²⁺ exchangers located in the t-tubule (3 Na⁺ exchanged for 1 Ca²⁺)

Question 10

How does the SERCA2 pump work?

Where is it located?

Answer 10

It’s located within the longitudinal SR (not the terminal cisternae). The Ca²⁺ ions (2 per pump cycle) move into the SR and diffuse to the terminal cisternae, where they bind to calsequestrin (low affinity, high capacity). Now they’re ready for the next action potential.

Question 11

Why does the SERCA2 pump dominate when it comes to calcium removal?

Answer 11

1) It’s located in the SR and the SR surrounds every myofibril (prime location)
2) Requires less energy (Vsr=0)

*In terms of housing, the SERCA2 pump has a better location and lower utilities than the NCX exchanger

Question 12

What drugs commonly target the DHPR and what are they used for?

Answer 12

Dyhydropyridines bind the DHPR (pretty self explanatory since DHPR stands for dihydropyridine receptor), and they are used as antihypertensive agents

Question 13

Which phase of the action potential leads to the termination of the ECC?

Answer 13

Phase 3, the repolarization phase shuts the calcium channels

Question 14

What is the principle subunit of the DHPR? How many repeats of it are there?

Answer 14

Cav 1.2

There are 4 repeats of this subunit

Question 15

Which 2 subunits are associated with the Cav 1.2 subunits of the DHPR?

Answer 15

A beta subunit and an alpha2-delta subunit

Question 16

Look at the attached image. If you can explain all of the processes, you’re in good shape.

Answer 16

Question 17

List the major ways that cardiac and skeletal muscle differ from eachother in terms of ECC.

Answer 17

1) Cardiac muscle requires extracellular calcium to enter and start process
2) Carciac muscle has Cav 1.2 subunit, skeletal has Cav 1.1 (as well as a gamma subunit that cardiac doesn’t)
3) Cardiac has RyR2 (requires extracellular calcium), skeletal has RyR1

Question 18

T or F?

The calcium/sodium exchanger (NCX) works bi-directionally

Bonus

What movement is occuring during repolarization?

Answer 18

True.

During repolarization, calcium is being effluxed (pumped out) and sodium is being pumped in

Question 19

What net charge is the result of the NCX and what effect does it have on the cell?

Answer 19

There’s a net +1 charge with each pump cycle, and as a result it slightly depolarizes the cell with each pump

Question 20

What impact does PKA have on ECC?

Answer 20

1) It phosphorylates the DHPR which leads to an increase in amplitude of the Ca current.
2) RyR2 gets phosphorylated and is activated more readily
3) Phosphorylation makes PLB (which normally inhibits SERCA2) to dissociate from SERCA2, allowing it to pump more Calcium faster which speeds relaxation
4) Troponin phosphorylation makes calcium get off of it faster.