Session 4 Flashcards
Which of the following calcium regulating proteins is a PMCA channel?
A. The channel on the sarcoplasmic reticulum that transports calcium from the cell cytoplasm to the cell endoplasmic reticulum
B. The channel on the cell membrane that transports calcium from the extracellular compartment to the intracellular cytoplasm of the cell
C. The bidirectional transport of calcium both in and out of the cell, on the cell membrane
D. The transport of calcium from the endoplasmic reticulum into the cytoplasm, via the sarcoplasmic reticulum
E. The channel on the cell membrane that transports calcium from the intracellular cytoplasm of the cell to the extracellular compartment
E - the only channel that is transporting calcium to the extracellular compartment in a unidirectional way.
A would be SERCA
B would be voltage/ligand/store-operated channel
C would be NCX
D would be RyR/IP3R
Which intracellular messenger acts to release calcium from the endoplasmic reticulum?
A - Ryanodine B - IP3 C - cAMP D - DAG E - GDP
B - IP3
IP3 acts on IP3 receptors located on endoplasmic reticulum to increase intracellular calcium concentration
Which GPCR subunit acts to increase intracellular calcium concentration?
A - Gαs B - Gβ C - Gαq D - Gαi E – Gγ
C - Gαq
Gαq acts on Phospholipase C to convert PIP2 to IP3, which in turn stimulates release of calcium into the cell via the IP3 receptors.
Following depolarisation of cardiac muscle and activation of VGCC, which of the following calcium channels is key in regulating CICR?
A. The channel on the sarcoplasmic reticulum that transports calcium from the cell cytoplasm to the cell endoplasmic reticulum
B. The channel on the cell membrane that transports calcium from the extracellular compartment to the intracellular cytoplasm of the cell
C. The bidirectional transport of calcium both in and out of the cell, on the cell membrane
D. The transport of calcium from the endoplasmic reticulum into the cytoplasm, via the sarcoplasmic reticulum
E. The channel on the cell membrane that transports calcium from the intracellular cytoplasm of the cell to the extracellular compartment
B - CICR acts by calcium entering the cell following VGCC, to activate ryanodine receptors on endoplasmic reticulum, increasing intracellular calcium concentration. B is the only channel releasing calcium from the endoplasmic reticulum.
A patient is given a drug that stimulates an M2 receptor. What effect would you expect to see on the levels of secondary messenger within the cell?
A – Decreased IP3 B – Increased cAMP C – Increased IP3 D – Decreased cAMP E – Increased DAG
D - Decreased cAMP
M2 receptors are coupled with a Gαi subunit (QISS QIQ). Therefore, adenylyl cyclase will be inhibited, causing a reduced concentration of cAMP.
Calcium sequestration and flow through cells is replete with abbreviations. Notate the full name of each abbreviation and state what the function of the protein is with respect to calcium homeostasis.
SER/SR VGCC SOC PMCA NCX SERCA CICR CaM
SER/SR - (Sarco)endoplasmic reticulum. Stores Ca2+ for rapid release.
VGCC - Voltage gated calcium channel. Rapid transport of Ca2+ into cells from extracellular space.
SOC - Store operated channel. Slow release of Ca2+ when all other sources have been depleted.
PMCA - Plasma membrane calcium ATPase. To quickly export Ca2+ back into the extracellular space. This is the main carrier of Ca2+ out of the cell; fine tunes intracellular calcium concentrations.
NCX - Sodium-calcium exchanger. The primary pump for expelling Ca2+ when intracellular concentrations are lowered by PMCA.
SERCA - Smooth/Sarco endoplasmic retiulum calcium ATPase. Used with NCX to rapidly re-establish Ca2+ gradients across the cell membrane, especially in excitable cells. It resides in the SER/ER and sends Ca2+ back into the cytoplasm.
CICR - Calcium induced calcium release. The process whereby ligand gated ion channel opening is linked via the ryanodine receptor to Ca2+ release by the SER/ER.
CaM - Calmodulin. Intracellular sensor of Ca2+ ion concentration (binds 4 ions) and modulates the activity of PMCA.
Contraction in smooth and cardiac muscle is primarily driven by Calcium Induced Calcium Release (CICR). Following membrane depolarisation, briefly outline the 4 main steps in CICR that lead to contraction. (Hint: The final step requires one protein to bind to another).
Membrane depolarisation --> (A) --> (B) --> Cytoplasm --> (C) --> Causing (D) to bind to (E) --> Muscle cell contraction
A: Ca2+ channels open allowing influx of calcium
B: Ryanodine receptors on the ER/SER are activated and more Ca2+ enters the cytoplasm
C: This causes a calcium ‘spark’.
D: The Ca2+ released into the cytosol allows actin filaments to bind to Troponin C, causing crossbridge cycling and contraction to occur
Indicate the typical concentration values of Ca2+ in each of the main compartments. Do this with what you think is the most appropriate relevant suffix i.e.: milli, micro or nanomolar. Use the exponential form next to this as well i.e. 10 -M (M= molarity).
Extracellular fluid [Ca2+]o?
Intracellular cytosolic component [Ca2+]i?
SER/SR* compartment [Ca2+]SER/SR?
*Approximate upper value is fine
Also, determine what the proportionate concentration difference in Ca2+ between extracellular fluid and the cytosol the main compartments?
Extracellular fluid = 1 milliM/10^-3 M
Intracellular cytosolic component = 100 nanoM/10^-7 M
SER/SR compartment: 1 milliM/10^-3 M
Proportionate difference: 10,000-fold.
This can be calculated by the difference in exponents i.e. 10^-3 / 10^-7 = 10^4 or 10,000
