5. Calcium homeostasis

Question 1

plasma membrane Na+/Ca2+ antiport (NCX, Na/Ca coupled transport)

Answer 1

Electrogenic, secondary active transporter located in the cytoplasm membrane. 3 Na+ are transported into the cell according to their electrochemical gradient and 1 Ca2+ is transported out of the cytosol against its electrochemical gradient during a duty cycle of the transporter. The transporter is powered by the electrochemical gradient of Na+. NCX is very important in cardiac myocytes where this transporter restores the resting Ca2+ concentration following a Ca2+ signal. The Na+ electrochemical gradient, which is necessary for the export of Ca2+ is maintained by the Na+/K+-ATPase in the cell membrane.

Question 2

plasma membrane Ca2+ ATP-ase (PMCA)

Answer 2

Electroneutral, primary active transporter, P-type ATP-ase, located in the cytoplasm membrane. 1 Ca2+-is transported from the cytosol to the extracellular space against its electrochemical gradient, accompanied by the inward transport of 2 H+ during one duty cycle. It is important in maintenig the resting cytosolic free Ca2+ concentration in mammalian cells.

Question 3

SERCA

Answer 3

Sarco-endoplasmatic reticulum Ca2+ ATP-ase, primary active, P-type ATP-ase transporter located in the membrane of the sarcoplasmic and endoplasmic reticulum. The transporter transports 1 Ca2+ from the cytosol into the lumen of the ER/SR at the cost of the hydrolysis of 1 ATP. SERCA contributes to the maintenance of the resting cytosolic Ca2+ concentration and to the restoration of the resting Ca2+ concentration following a Ca2+ signal.

Question 4

ryanodine receptor (RYR)

Answer 4

Intracellular ligand-gated Ca2+ channel located in the membrane of the sarcoplasmic and endoplasmic reticulum. The ligand activating the channel in skeletal muscle cells is a part of the DHP receptor (conformational coupling) whereas in cardiac myocytes and neurons the ligand is Ca2+ (CICR- Ca2+ induced Ca2+ release). Upon opening of the channel Ca2+ is released from the ER/SR store into the cytosol where the Ca2+ concentration concomitantly rises and leads to the specific cellular response (e.g. contraction of the muscle cells).

Question 5

IP3 receptor (IP3-R)

Answer 5

Intracellular ligand-gated Ca2+ channel located in the membrane of the endoplasmic reticulum. The ligand activating the channel is IP3 generated in the cell membrane upon receptor-ligand interaction. Upon opening of the channel Ca2+ is released from the ER store into the cytosol where the Ca2+ concentration concomitantly rises and leads to the specific cellular response (e.g. hormone secretion).

Question 6

calmodulin

Answer 6

Cytosolic Ca2+-binding protein with 4 Ca2+ binding pockets having EF-hand structure which cooperatively bind Ca2+. Depending on the Ca2+-saturation of the binding sites the conformation of calmodulin changes dramatically thereby enabling calmodulin to interact with and activate target proteins, such as the PMCA (plasma membrane Ca2+-ATP-ase) or the cytosolic protein kinases, CAM-kinase-II and MLC (myosin light chain kinase).