15 Questions
What are some of the properties of the calcium ion (Ca$^{2+}$) that make it useful as an intracellular second messenger?
Rapid, selective, reversible binding to proteins
What are some mechanisms by which Ca$^{2+}$ ions enter and exit the cell cytosol during the rising and falling phases of Ca$^{2+}$ signalling?
Voltage gated ion channels, ER/SR channels & triggers for rising phase; Buffers, Mitochondria, Ca$^{2+}$ extrusion for falling phase
What type of ligands can Ca$^{2+}$ bind well with?
Negatively charged oxygens (side chains of glutamate/aspartate) and uncharged oxygens (main-chain carbonyls and side chains of glutamine/asparagine)
How many ligands can Ca$^{2+}$ typically co-ordinate?
7-8 but up to 12
What are some important examples of cytoplasmic Ca$^{2+}$ sensors mentioned in the text?
Calmodulin, TnC, effectors
Which type of muscle has a functional dihydropyridine receptor (DHPR)?
Cardiac muscle
What proteins are involved in calcium removal from the cytoplasm?
Plasma membrane Ca2+ ATPase and sarco/endoplasmic reticulum Ca2+-ATPase
Which proteins modulate Ca2+ signals as cytosolic calcium buffers?
EF-hand proteins, parvalbumin, calbindin, and calretinin
Where is the mitochondrial Calcium Uniporter (MCU) located?
Outer mitochondrial membrane
What is the role of calcium signaling in cellular processes?
Vital for many cellular processes including muscle contraction and nitric oxide formation
What is the approximate concentration of free Ca$^{2+}$ in the blood?
1.25 mM
Where is the resting intracellular cytosolic Ca$^{2+}$ concentration kept very low?
50-100 nM
How is Ca$^{2+}$ signaling terminated?
By Ca-binding proteins such as calmodulin (CaM) and myosin light chain kinases, or by phosphatases such as myosin light chain phosphatase
What is the role of InsP3 in Ca$^{2+}$ signaling?
InsP3 is a global messenger that couples events at the plasma membrane to intracellular Ca-release
How does Ca$^{2+}$ enter or exit the cell cytosol?
Through ion channels or exchangers in the plasma membrane or internal stores
Study Notes
- Calcium (Ca2+) plays a crucial role in high affinity binding to irregular shaped pockets in proteins due to its flexible chemistry.
- Human body contains 1.2-1.4 kg of calcium, 99% of which is present as bone minerals.
- Approximately 1.5 g of calcium is present in the blood (~2.5 mM), with about half being free Ca2+.
- Extracellular Ca2+ is high (1.2 mM), while Ca2+ in intracellular stores such as the sarco/endoplasmic reticulum (SR/ER) is also high (1-2 mM).
- Resting intracellular cytosolic Ca2+ is kept very low (50-100 nM) to act as a second messenger.
- Diffusion of Ca2+ in the cytosol is very slow due to the complex sub-cellular architecture of cells.
- Ca2+ acts as a local messenger and is one of the most widespread signalling pathways used in mammalian cells and other organisms.
- Ca2+ enters or exits the cell cytosol through ion channels or exchangers in the plasma membrane or internal stores.
- Ca2+ transient increases can be generated by controlling the Ca2+ permeability of the plasma membrane or internal SR/ER membranes.
- InsP3 is a global messenger that couples events at the plasma membrane to intracellular Ca-release.
- Ca2+ signalling is essential for various functions such as fertilisation, contraction, secretion, metabolic changes, cell motility, gene expression, immune cell proliferation, and development.
- Ca2+ signalling is regulated by free [Ca2+] and various mechanisms such as InsP3 or RYR-evoked Ca2+ release.
- Ca2+ entering the cell can occur via tyrosine-kinase-linked receptors, G-protein-linked receptors, or smooth muscle voltage-sensitive Ca channels.
- Ca2+ signalling can be terminated by Ca-binding proteins such as calmodulin (CaM) and myosin light chain kinases, or by phosphatases such as myosin light chain phosphatase.
- Ca2+ is released from intracellular stores through ligand-gated ion channels in the ER membrane, or by the ryanodine receptor in the SR membrane.
- Ca2+ signalling is essential for various physiological processes such as muscle contraction and nerve impulse transmission.
- Ca2+ signalling is regulated by various signalling molecules such as phosphatidylinositol (4,5)-bisphosphate (PIP2), phospholipase C (PLC), and phosphatidylinositol 3-kinase (PI-3K).
- Ca2+ signalling is involved in various cellular responses to external stimuli, including the release of neurotransmitters, the regulation of gene expression, and the regulation of ion channels.
Test your knowledge about the properties and limitations of calcium ion (Ca2+) as an intracellular second messenger, and the mechanisms of Ca2+ signaling pathways in nature.
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