Calcium (Ca2+) plays a pivotal role in the physiology and biochemistry of organisms and the cell. It plays an important role in signal transduction pathways, where it acts as a second messenger, in neurotransmitter release from neurons, contraction of all muscle cell types, and fertilization. Many enzymes require calcium ions as a cofactor, those of the blood-clotting cascade being notable examples. Extracellular calcium is also important for maintaining the potential difference across excitable cell membranes, as well as proper bone formation.
Calcium levels in mammals are tightly regulated, with bone acting as the major mineral storage site. Calcium ions, Ca2+, are released from bone into the bloodstream under controlled conditions. Calcium is transported through the bloodstream as dissolved ions or bound to proteins such as serum albumin. Parathyroid hormone secreted by the parathyroid gland regulates the resorption of Ca2+ from bone, reabsorption in the kidney back into circulation, and increases in the activation of vitamin D3 to Calcitriol. Calcitriol, the active form of vitamin D3, promotes absorption of calcium from the intestines and the mobilization of calcium ions from bone matrix. Calcitonin secreted from the parafollicular cells of the thyroid gland also affects calcium levels by opposing parathyroid hormone; however, its physiological significance in humans is dubious.
Calcium storages are intracellular organelles, that constantly accumulate Ca2+ ions and release them during certain cellular events. Intracellular Ca2+ storages include mitochondria and the endoplasmic reticulum.
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In vertebrates, calcium ions, like many other ions, are of such vital importance to many physiological processes that its concentration is maintained within specific limits to ensure adequate homeostasis. This is evidenced by human plasma calcium, which is one of the most closely regulated physiological variables in the human body. Normal plasma levels vary between 1 and 2% over any given time. Approximately half of all ionized calcium circulates in its unbound form, with the other half being complexed with plasma proteins such as albumin, as well as anions including bicarbonate, citrate, phosphate, and sulfate.
Different tissues contain calcium in different concentrations. For instance, Ca2+ (mostly calcium phosphate and some calcium sulfate) is the most important (and specific) element of bone and calcified cartilage. In humans, the total body content of calcium is present mostly in the form of bone mineral (roughly 99%). In this state, it is largely unavailable for exchange/bioavailability. The way to overcome this is through the process of bone resorption, in which calcium is liberated into the bloodstream through the action of bone osteoclasts. The remainder of calcium is present within the extracellular and intracellular fluids.
Within a typical cell, the intracellular concentration of ionized calcium is roughly 100 nM, but is subject to increases of 10– to 100-fold during various cellular functions. The intracellular calcium level is kept relatively low with respect to the extracellular fluid, by an approximate magnitude of 12,000-fold. This gradient is maintained through various plasma membrane calcium pumps that utilize ATP for energy, as well as a sizable storage within intracellular compartments.
The effects of calcium on human cells are specific, meaning that different types of cells respond in different ways. However, in certain circumstances, its action may be more general. Ca2+ ions are one of the most widespread second messengers used in signal transduction. They make their entrance into the cytoplasm either from outside the cell through the cell membrane via calcium channels (such as Calcium-binding proteins or voltage-gated calcium channels), or from some internal calcium storages such as the endoplasmic reticulum and mitochondria. Levels of intracellular calcium are regulated by transport proteins that remove it from the cell. For example, the sodium-calcium exchanger uses energy from the electrochemical gradient of sodium by coupling the influx of sodium into cell (and down its concentration gradient) with the transport of calcium out of the cell. In addition, the plasma membrane Ca2+ ATPase (PMCA) obtains energy to pump calcium out of the cell by hydrolysing adenosine triphosphate (ATP). In neurons, voltage-dependent, calcium-selective ion channels are important for synaptic transmission through the release of neurotransmitters into the synaptic cleft by vesicle fusion of synaptic vesicles.
Calcium's function in muscle contraction was found as early as 1882 by Ringer. Subsequent investigations were to reveal its role as a messenger about a century later. Because its action is interconnected with cAMP, they are called synarchic messengers. Calcium can bind to several different calcium-modulated proteins such as troponin-C (the first one to be identified) and calmodulin, proteins that are necessary for promoting contraction in muscle.
| Cell type | Effect |
|---|---|
| secretory cells (mostly) | ↑secretion (vesicle fusion) |
| juxtaglomerular cell | ↓secretion[2] |
| Parathyroid chief cells | ↓secretion[2] |
| Neurons | transmission (vesicle fusion) |
| T cells | Activation in response to antigen presentation to the T cell receptor [3] |
| myocytes |
|
| Various | Activation of protein kinase C Further reading: Function of protein kinase C |
Substantial decreases in extracellular Ca2+ ion concentrations may result in a condition known as hypocalcemic tetany, which is marked by spontaneous motor neuron discharge. In addition, severe hypocalcaemia will begin to affect aspects of blood coagulation and signal transduction.
Ca2+ ions can damage cells if they enter in excessive numbers (for example, in the case of excitotoxicity, or over-excitation of neural circuits, which can occur in neurodegenerative diseases, or after insults such as brain trauma or stroke). Excessive entry of calcium into a cell may damage it or even cause it to undergo apoptosis, or death by necrosis. Calcium also acts as one of the primary regulators of osmotic stress (Osmotic shock). Chronically elevated plasma calcium (hypercalcemia) is associated with cardiac arrhythmias and decreased neuromuscular excitability. One cause of hypercalcemia is a condition known as hyperparathyroidism.
Some invertebrates use calcium compounds for building their exoskeleton (shells and carapaces) or endoskeleton (echinoderm plates and poriferan calcareous spicules).
When ABA signals the guard cells, free Ca2+ ions enter the cytosol from both outside the cell and internal stores, reversing the concentration gradient so the K+ ions begin exiting the cell. The loss of solutes makes the cell flaccid and closes the stomatal pores.
Calcium is a necessary ion in the formation of the mitotic spindle. Without the mitotic spindle, cellular division cannot occur. Although young leaves have a higher need for calcium, older leaves contain higher amounts of calcium because calcium is relatively immobile through the plant. It is not transported through the phloem because it can bind with other nutrient ions and precipitate out of liquid solutions.
Ca2+ ions are an essential component of plant cell walls and cell membranes, and are used as cations to balance organic anions in the plant vacuole.[4] The Ca2+ concentration of the vacuole may reach millimolar levels. The most striking use of Ca2+ ions as a structural element in plants occurs in the marine coccolithophores, which use Ca2+ to form the calcium carbonate plates, with which they are covered.
Calcium is needed to form the pectin in the middle lamella of newly formed cells.
Calcium is needed to stabilize the permeability of cell membranes. Without calcium, the cell walls are unable to stabilize and hold their contents. This is particularly important in developing fruits. Without calcium, the cell walls are weak and unable to hold the contents of the fruit.
Some plants accumulate Ca in their tissues, thus making them more firm. Calcium is stored as Ca-oxalate crystals in plastids.
Ca2+ ions are usually kept at nanomolar levels in the cytosol of plant cells, and act in a number of signal transduction pathways as second messengers.
Many protists make use of calcium.
The amount of calcium in blood (more specifically, in blood plasma) can be measured as total calcium, which includes both protein-bound and free calcium. In contrast, ionized calcium is a measure of free calcium. An abnormally high level of calcium in plasma is termed hypercalcemia and an abnormally low level is termed hypocalcemia, with "abnormal" generally referring to levels outside the reference range.
| Target | Lower limit | Upper limit | Unit |
| Ionized calcium | 1.03,[5] 1.10[6] | 1.23,[5] 1.30[6] | mmol/L |
| 4.1,[7] 4.4[7] | 4.9,[7] 5.2[7] | mg/dL | |
| Total calcium | 2.1,[8][9] 2.2[6] | 2.5,[9][6] 2.6,[9] 2.8[8] | mmol/L |
| 8.4,[8] 8.5[10] | 10.2,[8] 10.5[10] | mg/dL |
The total amount of Ca2+ present in a tissue may be measured using atomic absorption spectrometry, in which the tissue is vaporized and combusted. To measure Ca2+ concentration or spatial distribution within the cell cytoplasm in vivo, a range of fluorescent reporters may be used. These include cell permeable, calcium-binding fluorescent dyes such as Fura-2 or genetically engineered variant of green fluorescent protein (GFP) named Cameleon.
The USDA web site has a very complete table of calcium content (in mg) of common foods per common measures (link below).
Calcium amount in foods, 100 g:
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