Signaling: Ca2+ Flashcards Preview

Molecules to Medicine III > Signaling: Ca2+ > Flashcards

Flashcards in Signaling: Ca2+ Deck (20)
1

What are some of the cellular functions of calcium?

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

2

What are some pathophysiologic conditions involving calcium?

- ischemic cell death
- malignant hyperthermia
- central core disease
- cardia arrhythmias
- motor and cognitive disorders
- immune disorders
- hypertension
- neuropathic pain
- epilepsy

3

Why is calcium signaling more rapid than many other signals?

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

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

4

What are some sources and sinks of Ca2+?

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

5

What promotes movement of Ca2+ into cells?

1. Concentration Gradient:
2mM outside -> 100nm inside

2. Voltage across membrane:
resting potential of -60mV

6

How does Ca2+ move through ion channels?

Passively
- down electrochemical gradient

7

How does Ca2+ move through the plasma membrane?

Voltage and ligand gated channels
- nmda
- Ach
- move Ca2+ from out to in

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

8

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

IP3 receptors (lymphocytes)
Ryanodine receptors (muscle contraction)

Ca2+ from lumen to cytoplasm

9

How does Ca2+ move out of mitochondria?

Uniporter
Permiability transition pore

10

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

Passive! Down electrochemical gradient!

- ion channel
- voltage/ ligand gated channels
- IP3 receptors
- Ryanodine receptors
- Uniporter
- Permiability transition pore

11

What is the difference between a source and sink?

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

12

How does Ca2+ move out of cytoplasm?

Active, against electrochemical gradient!

- slowly (more work)

ATP pumps
Na+/Ca+ exchanges

13

How do ATP pumps move Ca2+?

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

14

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

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

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

15

What are Ca2+ buffers?

proteins that bind Ca2+

help to ensure localized signaling of Ca2+

16

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

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

How does Calsequestrin work?

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

What are Ca2+ effectors?

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

Why are C2 domains important Ca2+ binding domains

localize the proteins they are attached to to plasma membrane

20

Why is calmodulin important?

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