Calcium signalling Flashcards
Calcium (Ca2+)
- is a universal and ubiquitous intracellular messenger
- has the highest gradient across the membrane (at resting potential, there is more extracellular calcium)
Why is there less intracellular calcium levels at resting potential?
High concentrations of calcium are toxic to the cytosol
Calcium stores in the cell
Is stored in the lumen cells and nuclear envelope and released when needed through receptors of voltage-gated Ca2+ channels
What does the cell do regarding high calcium levels?
It removes calcium to maintain a regular low cytosolic Ca2+ concentration
Method 1 - removing calcium out of the cell
Uses pumps to remove Ca out of the cell
Plasma membrane PMCA pumps (calcium/ATPase)
In: 2H
Out: 1Ca
Energy used: 1ATP
Exchanger: Ca K/Na pump
In: 4Na
Out: 1Ca and 1K
Exchanger: Ca/Na pump
In: 3Na
Out: 1Ca
Method 2 - Sequestering Calcium into intracellular stores
Calcium is stores in endoplasmic reticulum (ER) or sarcoplasmic reticulum (SR) and other organelles such as nuclear envelope, endosomes, lysosomes and mitochondira
Why does the cell need to have adequate calcium stores?
Inadequate storage can lead to cell remodelling transformations into malignant cells
What is the main storage of calcium?
Endoplasmic reticulum
What is the SERCA pump?
SarcoEndo reticulum calcium ATPase pump
MCU
Mitochondria calcium uniporter which is active when Ca hits 1yl. Pumps Ca from cytosol into mitochondrial matrix for temporary removal
Method 3 - chelating calcium using calcium binding proteins
buffers (e.g calbindin and calquestrin) in the cytosol bind to calcium to prevent Ca ion mobility
Calcium sensors e.g protein kinase C
catch calcium and bind directly until the cell resolves its gradient
Units of calcium signalling mechanism
Stimulus > generation of calcium mobilising signals > ON mechanism
How do our cells use Calcium in signalling?
Skeletal muscle, neurones, pancreatic acinar cells
Use in skeletal muscles
calcium is released from the SR and interacts with sensors to trigger contraction and synthesise glucose and ATP for energy
= contraction
Use in neurones
produces localised pulse of calcium signal to trigger exocytosis = mobilises Ca from ER
Use in pancreatic acinar cells
in the pancreas, calcium activates secretion
What is the difference in Ca use between skeletal muscle and neurons, and in the pancreas?
The pancreas in non-excitable and don’t have voltage gated calcium ion channels = they require a stimuli to produce secondary messengers and release Ca stores
Ca2+ entry in excitable cells
- Calcium enters through voltage gated channels
- Second messengers of electrical signalling initiate different cellular events
Ca2+ entry in non-excitable cells
- Calcium enters through Ca2+ stores which are activated in response to low Ca2+ levels
Why are physiological Ca2+ spikes localised in the pancreatic acinar cells?
The spikes occur in the secretory granule, which is surrounded by mitochondria - take up Ca2+ during calcium release. Mitochondria also release ATP where it’s needed after Ca release
