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Molecules to Medicine III > Signaling: Ca2+ > Flashcards

Signaling: Ca2+ Flashcards

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Organic Chemistry 101 flashcards
1
Q

What are some of the cellular functions of calcium?

A

UBIQUITOUS

  • gene expression
  • programmed cell death
  • Mitochondrial ATP synthesis

CELL SPECIFIC

  • T - Lymphocyte activation
  • Sperm capacitation, block of polyspermy
  • neurotransmitter and hormone release
  • neurite outgrowth
  • electrical signaling
  • striated muscle contraction
  • smooth muscle contraction
  • smooth muscle relaxation
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2
Q

What are some pathophysiologic conditions involving calcium?

A
  • ischemic cell death
  • malignant hyperthermia
  • central core disease
  • cardia arrhythmias
  • motor and cognitive disorders
  • immune disorders
  • hypertension
  • neuropathic pain
  • epilepsy
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3
Q

Why is calcium signaling more rapid than many other signals?

A

Not generated by catalytic enzymes
=> RECRUITED FROM SINKS/ SOURCES

([100nm] intracellular v. [2mM]

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4
Q

What are some sources and sinks of Ca2+?

A

source = sink

  • Extracellular space 2mM [Ca2+]
  • S and R ER (sarcoplasmic reticulum)
  • Nuclear envelope - esp reg gene expression
  • Mitochondria
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5
Q

What promotes movement of Ca2+ into cells?

A
  1. Concentration Gradient:
    2mM outside -> 100nm inside
  2. Voltage across membrane:
    resting potential of -60mV
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6
Q

How does Ca2+ move through ion channels?

A

Passively

- down electrochemical gradient

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7
Q

How does Ca2+ move through the plasma membrane?

A

Voltage and ligand gated channels

  • nmda
  • Ach
  • move Ca2+ from out to in

Store operated:
activated by decrease in intracellular [Ca2+]

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8
Q

How does Ca2+ move through ER/SR/ nuclear envelope?

A 
IP3 receptors (lymphocytes)
Ryanodine receptors (muscle contraction)

Ca2+ from lumen to cytoplasm

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9
Q

How does Ca2+ move out of mitochondria?

A

Uniporter

Permiability transition pore

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10
Q

What are the ways Ca2+ can move out of sinks into the cytoplasm?

A

Passive! Down electrochemical gradient!

  • ion channel
  • voltage/ ligand gated channels
  • IP3 receptors
  • Ryanodine receptors
  • Uniporter
  • Permiability transition pore
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11
Q

What is the difference between a source and sink?

A

Same thing - depends on relative movement of Ca2+
Sink: drains/ gets rid of
Source: supplies Ca2+ to cytoplasm

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12
Q

How does Ca2+ move out of cytoplasm?

A

Active, against electrochemical gradient!

  • slowly (more work)

ATP pumps
Na+/Ca+ exchanges

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13
Q

How do ATP pumps move Ca2+?

A

use ATP to move Ca2+ out of cytoplasm into:
ER/SR/ nuclear envelope (SERCa - ER/SR)
OR
Extracellular space (PM - plasma membrane: ATP-> ADP)

ACTIVE TRANSPORT

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14
Q

How do Na+/Ca+ echangers move Ca2+?

A

out across plasma membrane
OR
from mitochondria into cytoplasm (only if [cytoplasm] lower than [mitochondria])

3Na+/1Ca2+
(get E from Na+ gradient)

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15
Q

What are Ca2+ buffers?

A

proteins that bind Ca2+

help to ensure localized signaling of Ca2+

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16
Q

How do Ca2+ buffers work to affect cytoplasmic Ca2+ signals?

A

ex) Parvalbumin

  • restrict spatial and temporal spread of Ca2+
    (slow diffusion of large release of Ca2+)
  • Temporary storage of Ca2+
    (exudation is slow- prevent generation of large E gradient)
17
Q

How does Calsequestrin work?

A

Many Ca2+ binding sites
=> store a lot of Ca2+ in ER/SR by binding so it can’t contribute to electrochemical gradient

  • high capacity
  • low affinity (so Ca2+ can exit as needed)
18
Q

What are Ca2+ effectors?

A

surface membrane potential

  • change polarization
  • activate Ca2+ activated channels

Protein Kinase C (PKC)
- translocate to membrane

Synaptotagmin
- Ca2+ dependent fusion of synaptic vesicles

Calmodulin
- multiple downstream targets

19
Q

Why are C2 domains important Ca2+ binding domains

A

localize the proteins they are attached to to plasma membrane

20
Q

Why is calmodulin important?

A

4 EF hands (2 at each end)
- Ca2+ binds here -> conformational change (dumbell to pac man) -> grab onto domains

Regulate: 
ion channels 
protein kinases
phosphatases 
cyclic nucleotide phosphodiesterases

Molecules to Medicine III (28 decks)

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