Calcium homeostasis part 2 (week 5)

Question 1

what is the function of Ca2+ ATPases (calcium pumps)

Answer 1

enzymes responsible for actively transporting calcium ions across cell membranes against their concentration gradient

Question 2

explain the mechanism of the Ca2+ ATPases

Answer 2

uses energy derived from the hydrolysis of ATP to pump calcium ions out of the cytoplasm, contributing to the maintenance of low intracellular calcium levels

Question 2

where does the Ca2+ ATPases work

Answer 2

found on the plasma membrane of orgenelles such as the endoplasmic reticulum and sarcoplasmic reticulum

Question 3

what is the importance of the Ca2+ ATPases

Answer 3

by actively removing the calcium from the cytoplasm, Ca2+ ATPases play crucial role in preventing excessive accumulation of calcium within the cell, which could lead to unwanted cellular activities

Question 3

what is the function of Na+/ Ca2+ exchangers

Answer 3

these are membrane transport proteins that exchange sodium ions for calcium ions across the cell membrane

Question 4

where are the Na+/ Ca2+ exchangers located

Answer 4

plasma membrane of cells

Question 5

explain the mechanism of the Na+/ Ca2+ exchangers

Answer 5

they utilise the sodium gradient created by the sodium potassium pump (Na+/K+) to extrude calcium ions from the cell. For every three sodium ions pumped in, once calcium ion is pumped out

Question 6

explain the importance of Na+/ Ca2+ exchangers

Answer 6

they contribute to the regulation of basal Ca2+ levels by counteracting the entry of calcium into the cell through various channels. They are especially important during the recovery phase after a cellular event that causes a transient increase in intracellular calcium.

Question 7

name some proteins within the cytoplasm

Answer 7

calmodulin: (calcium binding protein) function is regulating various cellular processes by interacting with and modulating the activity of target proteins in response to changes in intracellular calcium levels.

troponin: found in muscle cells
involved in muscle contractions. Troponin C, one of its subunits, binds calcium, allowing for the regulation of muscle contraction in response to changes in cytoplasmic calcium concentrations.

Question 8

name some proteins within intracellular organelles

Answer 8

Calreticulin and Calsequestrin (Endoplasmic Reticulum)

Question 9

what does calreticulin do

Answer 9

calcium-binding chaperone protein involved in protein folding within the ER. Helps buffer calcium levels within the ER lumen.

Question 10

what does calsequestrin do

Answer 10

binds and stores calcium in the sarcoplasmic reticulum of muscle cells, releasing it upon stimulation for muscle contraction.

Question 11

what are the major points of entry of Ca2+

Answer 11

Ca2+ ATPases
* ATP2B (plasma membrane), ATP2A (endoplasmic/sarcoplasmic reticulum) and ATP2C (Golgi)
Voltage-gated Ca2+ channels
* L-type calcium channels
Na+/Ca2+ exchanger
* NCX1, NCX2 and NCX3
Permeability transition pore

Question 12

what are the two types of Ca2+ ATPase

Answer 12

Plasma membrane Ca2+ ATPase(PMCA)
1:1 H+ and Ca2+
Sarcoplasmic reticulum Ca2+ ATPase (SERCA)
2:2 H+ and Ca2+

Question 13

describe the Plasma membrane Ca2+

Answer 13

PMCA moves 1 Ca2+ out of the cell for each ATP hydrolysed
Activity can be increased by the binding of calmodulin to the c terminal domain
Encoded by the 4 genes (ATP2B1-4) of which you get 4 splice variants (PMCA1-4)

Question 14

describe the Sarcoplasmic reticulum Ca2+ ATPase

Answer 14

SERCA moves 2 Ca2+ into the sarcoplasmic reticulum for each ATP hydrolysed

Question 15

what are the two main stages in the SERCA

Answer 15

E1- high calcium affinity
E2 - low calcium affinity

activity can be regulated by ATP and phospholamban (PLN)

Encoded by the 3 genes (ATP2A1-3) from which you get multiple splice variants

Question 16

what are the 4 subunits for the voltage gated Ca2+ channels

Answer 16

α1 subunit - largest subunit. Contains the ion selective residues (glutamine) and the voltage sensor (lysine or arginine)
β subunit - intracellular subunit. Expression, membrane trafficking and regulation i.e. amplitude of Ca2+ current and activation/ inactivation kinetics
α2δ - extracellular subunit. Two proteins joined by disulphide bridges. Smaller effect on kinetics andCa2+ current amplitude
γ - variable effects on channel function

Question 17

what are voltage gated calcium channels alpha encoded by

Answer 17

CACNA1

Question 18

where is Cav1

Answer 18

L-type channels (skeletal muscle, smooth muscle, cardiac muscle, secretory tissues and nervous system)

Question 19

Cav2

Answer 19

P/Q-type Ca2+ channels
N-type Ca2+ channels
R-type Ca2+ channels (nervous system)

Question 20

Cav3

Answer 20

T-type Ca2+ channels (neurons and the heart for pacemaker activity)

Question 21

Ca2+ release from intracellular stores like ER rely on the activation of what

Answer 21

1,4 T-Triphosphate receptors (IP3R) in the membrane of the ER

IP3R are tetramers of 4 transmembrane spanning

Question 22

what are the key proteins that Store-operated calcium entry relies on

Answer 22

STIM1 and Orai

Question 23

Explain the process of STIM1 and Orai

Answer 23

STIMs are single-pass transmembrane protein that sense the changes of ER luminal Ca2+ levels.
* Upon Ca2+ store-depletion, STIM1 proteins undergo oligomerisation and translocation to ER/SR-PM (known as puncta formation),
* This attracts the plasma membrane Orai1 to the same site =interaction
* Channel activation and opening of these channels facilitating movement of Ca2+ into the cell