calcium signaling Flashcards

1
Q

Cytoplasmic Ca2+ buffers are proteins that bind to

A

free Ca2+ in the cell.

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2
Q

cytoplasmic Ca2+ protein buffers function to

A

restrict the spatial spread of free Ca2+ in order to localize calcium and control signaling pathways that depend upon calcium concentrations.

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3
Q

Buffers also store:

A

Ca2+ until it can be properly transported

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4
Q

After calcium ions are released from their effectors, buffers sequester them until they are

A

transported out of the cell, which is a relatively slow process.

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5
Q

Calcium ions are released from the ER/SR into the cytoplasm through

A

calcium channels mediated by ryanodine and inositol triphosphated (IP3) receptors.

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6
Q

Recognition of Ca2+ in the cytoplasm by _____ receptors triggers the ____.

A

ryanodine

release of Ca2+ from the ER/SR

This is a positive feedback mechanism:

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7
Q

the release of calcium ions is sensed by the receptors, leading to _____.

A

further calcium release

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8
Q

IP3 receptors respond to

A

IP3 (a secondary messenger in a G-coupled protein receptor signaling pathway) to activate Ca2+ channels and stimulate Ca2+ influx into the cytoplasm from the ER/SR.

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9
Q

Calcium ions are extruded from cytoplasm into the extracellular space or the lumen of the ER/SR

A

by Ca2+ pumps that hydrolyze ATP.

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10
Q

Ca2+ pump is called:

  • In cell membrane:
  • In the SR/ER:
A

Plasma Membrane Ca2+ ATPase (PMCa ATPase)

Sarco/Endoplamic Reticulum Ca2+ ATPase
(SERCa ATPase).

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11
Q

EF hands and C2 domains are _____.

A

structural motifs that depend on coordination with calcium ions

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12
Q

EF hand structure:

A

EF hands are helix-loop-helix domains with two perpendicular alpha helices connected by a short loop that coordinates with calcium ions.

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13
Q

Calmodulin is a protein made up of

A

4 EF hands

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14
Q

C2 domains are

A

structural domains on proteins that target the protein to the cell membrane.

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15
Q

______ has a C2 domain.

A

Protein Kinase A

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16
Q

The C2 domain coordinates with

A

2 or 3 calcium ions.

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17
Q

Other calcium ion effectors have

A

EF-hand domains and many other proteins that bind with plasma membranes contain C2 domains (such as synaptotagmin ,which is involved in neurotransmitter release).

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18
Q

synaptotagmin is involved in

A

neurotransmitter release

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19
Q

Fundamentals governing calcium as a cell signal

A
  1. Sources and Sinks for Calcium
  2. Movements in/out of Sources/Sinks
  3. Cellular Calcium Buffers
  4. Calcium Effectors
20
Q

onset of Ca2+ signals is ____

A

far more rapid than that of other signals.

21
Q

Movement from sources into cytoplasm

A
  1. Ion Channels
  2. Plasma membrane:
  3. ER/SR, (nuclear envelope):
  4. Mitochondria
22
Q

Movement of sources of Calcium Ion Channels

A

move passive, electrochemically downhill

23
Q

Movement of sources of Calcium:

Plasma Membrane

A
  1. Voltage- and ligand-gated Ca2+ channels
  2. store-operated Ca2+ channels (Orai1).
  3. Ca2+ moves from outside cell into cytoplasm
24
Q

Movement of sources of calcium: ER/SR (nuclear envelope):

A
  1. IP3 receptors
  2. ryanodine receptors.
  3. Ca2+ moves from lumen of ER/SR to cytoplasm
25
Movement of sources of calcium: Mitochondria
1. Mitochondrial uniporter 2. permeability transition pore (MPTP) 3. Direction depends on Ca2+ gradient. 4. MPTP contributes to cell death during stroke and myocardial infarction.
26
Movement from cytoplasm into sinks
1. Transporters (active, against electrochemical gradient) 2. Ca2+ pumps use ATP to move Ca2+ out of cytoplasm into extracellular space (PMCA pumps) or into lumen of ER/SR (SERCA pumps) 3. Na+/Ca2+ exchangers extrude Ca2+ out across plasma membrane or from mitochondria into cytoplasm.
27
NCX exchanges {3 Na+}:{1 Ca2+}, deriving energy from
Na+ gradient.
28
Cytoplasmic buffers restrict the ______ and create _____
spatial spread of Ca2+ distinct signaling domains
29
Effectors
1. Surface Membrane Potential 2. Protein Kinase C 3. Synaptotagmin 4. Calmodulin (multiple downstream targets)
30
Surface Membrane Potential
Ca2+ channels, Ca2+-activated channels | (Neuronal bursting, cardiac pacemaking)
31
Protein Kinase C
(Translocation to the membrane)
32
Synaptotagmin
(Ca2+-dependent fusion of synaptic vesicles)
33
Calmodulin
(multiple downstream targets)
34
Binding of Ca2+ causes C2 domains to
associate with the plasma membrane
35
Calmodulin binds to and confers
Ca2+ regulation to a large number of other proteins, including ion channels, protein kinases and phosphatases, and cyclic nucleotide phosphodiesterases.
36
The EF-hand motif of calmodulin is found in
many other Ca2+ effectors, including parvalbumin (a cellular Ca2+ buffer), calpain (a Ca2+-activated protease) and troponin.
37
There are also many Ca2+-binding motifs that
do not resemble C2 domains or EF hands.
38
sources of calcium:
1. ER/SR 2. extra cellular 3. nuclear envelope 4. mitochondria
39
Transporters calcium Movements are much _____than via ion channels
slower
40
Na+/Ca2+ exchangers (NCX, RetX) function:
extrude Ca2+ out across plasma membrane or from mitochondria into cytoplasm. NCX exchanges {3 Na+}:{1 Ca2+}, deriving energy from Na+ gradient.
41
The cytoplasmic buffers (e.g., parvalbumin) restrict the _______
spatial and temporal spread of Ca2+.
42
The cytoplasmic buffers serve as a ______
temporary storage site for Ca2+ while the relatively slow transport processes are operating.
43
effectors: (4)
An effector is how calcium does something: 1. surface membrane potential 2. protein kinase C 3. synaptotagmin 4. Calmodulin
44
Effector: surface membrane potential
can do this directly: Ca2+ channels, Also hyper polarized: Ca2+-activated channels (Neuronal bursting, cardiac pacemaking)
45
Effector: Protein Kinase C
Activated by calcium or diacylglycerol | Translocation to the membrane
46
Effector: Synaototagmin
Ca2+ dependent fusion of synaptic vesicles
47
Binding of Ca2+ causes C2 domains to
associate with the plasma membrane