Flashcards in Signaling: Ca2+ Deck (20)
What are some of the cellular functions of calcium?
- gene expression
- programmed cell death
- Mitochondrial ATP synthesis
- 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
What are some pathophysiologic conditions involving calcium?
- ischemic cell death
- malignant hyperthermia
- central core disease
- cardia arrhythmias
- motor and cognitive disorders
- immune disorders
- neuropathic pain
Why is calcium signaling more rapid than many other signals?
Not generated by catalytic enzymes
=> RECRUITED FROM SINKS/ SOURCES
([100nm] intracellular v. [2mM]
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
What promotes movement of Ca2+ into cells?
1. Concentration Gradient:
2mM outside -> 100nm inside
2. Voltage across membrane:
resting potential of -60mV
How does Ca2+ move through ion channels?
- down electrochemical gradient
How does Ca2+ move through the plasma membrane?
Voltage and ligand gated channels
- move Ca2+ from out to in
activated by decrease in intracellular [Ca2+]
How does Ca2+ move through ER/SR/ nuclear envelope?
IP3 receptors (lymphocytes)
Ryanodine receptors (muscle contraction)
Ca2+ from lumen to cytoplasm
How does Ca2+ move out of mitochondria?
Permiability transition pore
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
- Permiability transition pore
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
How does Ca2+ move out of cytoplasm?
Active, against electrochemical gradient!
- slowly (more work)
How do ATP pumps move Ca2+?
use ATP to move Ca2+ out of cytoplasm into:
ER/SR/ nuclear envelope (SERCa - ER/SR)
Extracellular space (PM - plasma membrane: ATP-> ADP)
How do Na+/Ca+ echangers move Ca2+?
out across plasma membrane
from mitochondria into cytoplasm (only if [cytoplasm] lower than [mitochondria])
(get E from Na+ gradient)
What are Ca2+ buffers?
proteins that bind Ca2+
help to ensure localized signaling of Ca2+
How do Ca2+ buffers work to affect cytoplasmic Ca2+ signals?
- 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)
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)
What are Ca2+ effectors?
surface membrane potential
- change polarization
- activate Ca2+ activated channels
Protein Kinase C (PKC)
- translocate to membrane
- Ca2+ dependent fusion of synaptic vesicles
- multiple downstream targets
Why are C2 domains important Ca2+ binding domains
localize the proteins they are attached to to plasma membrane