Calcium Signaling Flashcards
Why are Ca2+ transporters relatively slow and what are the two primary types of transporters?
Transporters move ions against their electrochemical gradient, so they must perform work to achieve their goals. This makes their action slow in comparison to channels that allow flow down the gradients. Ca2+ pumps use active transport to move Ca2+ ions out of the cytoplasm into the ECF or internal stores (ER, SR, NM called SERCa ATPase) by hydrolyzing ATP. Na+/Ca2+ exchangers allow 3 Na+ to flow down its electrochemical gradient into the cell in order to push 1 Ca2+ up its electrochemical gradient into the ECF.
What are two calcium buffers, where do they localize, and how do they function?
In the cytoplasm, parvalbumin restricts the spatial and temporal spread of Ca2+ ions, requiring larger doses of Ca2+ to actually trigger a signal or allowing for the creation of different local signaling affects within one cell. They also serve as temporary storage sites while the slow transport processes continue, allowing for muscle relaxation after a contraction signal. In the ER/SR, calsequestrin has a very large Ca2+ storage capacity and relatively low affinity, allowing the storage of large quantities of Ca2+ without the creation of large concentration gradients, and rapid release when triggered due to the low affinity.
Four common and important Ca2+ related effector targets.
Surface membrane potential, Ca2+ can cause depolarization and action potentials, as well as hyper polarization due to Ca2+Gated K+ channels.
Protein Kinase C (PKC) Causes translocation to the membrane.
Synaptotagmin (Ca2+ dependent fusion of synaptic vesicles)
Calmodulin (multiple downstream targets)
What protein domains do Ca2+ ions bind to and what are two examples of proteins with these domains?
Ca2+ binds to C2 domains. These domains are found on PKC (where they got their “C” name from) and synaptotagmin which has 2 C2 (a&b) domains near its transmembrane domain.
What is another protein domain that Ca2+ ions may bind to on calmodulin?
The “EF Hand” domain. There are also many other sorts of domains that Ca2+ may bind to in other proteins.
How does Ca2+ trigger both muscle contraction and relaxation?
VGCa2+ channels in the plasma membrane cause global increase in cytoplasmic Ca2+ opening RyRs which triggers additional Ca2+ release and causes muscle contraction. There are also ligand-gated Ca2+ channels on the SR/ER that are located very near Ca2+-gated K+ channels. Activation of these Ca2+ channels allows K+ influx, causing hyper polarization of cell and closing VGCa2+ channels, leading to muscle relaxation. This is all facilitated by the Ca2+ buffer system that allows for localized Ca2+ signaling.
How can a decrease in extracellular Ca2+ concentration or a mutation in store-dependent Ca2+ channels cause immune deficiency?
Helper T-lymphocytes are activated by the following chain:
MHC binds to T-cell receptors
T-cell receptors trigger Tyrosine kinases
Tyrosine kinases activate PLC->PIP2->IP3 & DAG
IP3 activates IP3 receptor Ca2+ channels in ER/SR, leading to Ca2+ store depletion
Store depletion releases Stim1 to trigger Store-dependent Channels like Orai1.
Thus, decreased ECF Ca2+ or mutant Store-dependent channels will not allow the Helper T-cells to activate.
