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
Q

Movement of sources of calcium: Mitochondria

A
  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
Q

Movement from cytoplasm into sinks

A
  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
Q

NCX exchanges {3 Na+}:{1 Ca2+}, deriving energy from

A

Na+ gradient.

28
Q

Cytoplasmic buffers restrict the ______ and create _____

A

spatial spread of Ca2+

distinct signaling domains

29
Q

Effectors

A
  1. Surface Membrane Potential
  2. Protein Kinase C
  3. Synaptotagmin
  4. Calmodulin (multiple downstream targets)
30
Q

Surface Membrane Potential

A

Ca2+ channels, Ca2+-activated channels

(Neuronal bursting, cardiac pacemaking)

31
Q

Protein Kinase C

A

(Translocation to the membrane)

32
Q

Synaptotagmin

A

(Ca2+-dependent fusion of synaptic vesicles)

33
Q

Calmodulin

A

(multiple downstream targets)

34
Q

Binding of Ca2+ causes C2 domains to

A

associate with the plasma membrane

35
Q

Calmodulin binds to and confers

A

Ca2+ regulation to a large number of other proteins, including ion channels, protein kinases and phosphatases, and cyclic nucleotide phosphodiesterases.

36
Q

The EF-hand motif of calmodulin is found in

A

many other Ca2+ effectors, including parvalbumin (a cellular Ca2+ buffer), calpain (a Ca2+-activated protease) and troponin.

37
Q

There are also many Ca2+-binding motifs that

A

do not resemble C2 domains or EF hands.

38
Q

sources of calcium:

A
  1. ER/SR
  2. extra cellular
  3. nuclear envelope
  4. mitochondria
39
Q

Transporters calcium Movements are much _____than via ion channels

A

slower

40
Q

Na+/Ca2+ exchangers (NCX, RetX) function:

A

extrude Ca2+ out across plasma membrane or from mitochondria into cytoplasm. NCX exchanges {3 Na+}:{1 Ca2+}, deriving energy from Na+ gradient.

41
Q

The cytoplasmic buffers (e.g., parvalbumin) restrict the _______

A

spatial and temporal spread of Ca2+.

42
Q

The cytoplasmic buffers serve as a ______

A

temporary storage site for Ca2+ while the relatively slow transport processes are operating.

43
Q

effectors: (4)

A

An effector is how calcium does something:

  1. surface membrane potential
  2. protein kinase C
  3. synaptotagmin
  4. Calmodulin
44
Q

Effector: surface membrane potential

A

can do this directly:
Ca2+ channels,

Also hyper polarized: Ca2+-activated channels

(Neuronal bursting, cardiac pacemaking)

45
Q

Effector: Protein Kinase C

A

Activated by calcium or diacylglycerol

Translocation to the membrane

46
Q

Effector: Synaototagmin

A

Ca2+ dependent fusion of synaptic vesicles

47
Q

Binding of Ca2+ causes C2 domains to

A

associate with the plasma membrane