# Calcium buffering

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{{Short description|Cellular process}}
'''Calcium buffering''' describes the processes which help stabilise the concentration of free calcium ions within cells, in a similar manner to how [pH buffers](/source/Buffer_solution) maintain a stable concentration of hydrogen ions.<ref>{{cite book | vauthors = Gilabert JA | chapter = Cytoplasmic Calcium Buffering | title = Calcium Signaling | volume = 740 | pages = 483–98 | year = 2012 | pmid = 22453955 | doi = 10.1007/978-94-007-2888-2_20 | isbn = 978-94-007-2887-5 | series = Advances in Experimental Medicine and Biology }}</ref>  The majority of calcium ions within the cell are bound to intracellular proteins, leaving a minority freely dissociated.<ref name=":0">{{Cite book|title=Excitation-contraction coupling and cardiac contractile force|last=M.|first=Bers, D.|date=2001|publisher=Kluwer Academic Publishers|isbn=978-0-7923-7158-8|edition=2nd|location=Dordrecht|oclc=47659382}}</ref>  When calcium is added to or removed from the cytoplasm by transport across the [cell membrane](/source/cell_membrane) or [sarcoplasmic reticulum](/source/sarcoplasmic_reticulum), calcium buffers minimise the effect on changes in cytoplasmic free calcium concentration by binding calcium to or releasing calcium from intracellular proteins.  As a result, 99% of the calcium added to the cytosol of a cardiomyocyte during each cardiac cycle becomes bound to calcium buffers, creating a relatively small change in free calcium.<ref name=":0" />

The regulation of free calcium is of particular importance in excitable cells like [cardiomyocytes](/source/Cardiac_muscle_cell)<ref>{{cite journal | vauthors = Smith GL, Eisner DA | title = Calcium Buffering in the Heart in Health and Disease | journal = Circulation | volume = 139 | issue = 20 | pages = 2358–2371 | date = May 2019 | pmid = 31082292 | pmc = 6520234 | doi = 10.1161/CIRCULATIONAHA.118.039329 }}</ref> and [neuron](/source/neuron)s.<ref>{{cite journal | vauthors = Schwaller B | title = Cytosolic Ca2+ buffers | journal = Cold Spring Harbor Perspectives in Biology | volume = 2 | issue = 11 | article-number = a004051 | date = November 2010 | pmid = 20943758 | pmc = 2964180 | doi = 10.1101/cshperspect.a004051 }}</ref> Within these cells, many intracellular proteins can act as calcium buffers.  In cardiac muscle cells, the most important buffers within the cytoplasm include [troponin C](/source/troponin_C), [SERCA](/source/SERCA), [calmodulin](/source/calmodulin), and [myosin](/source/myosin), while the most important within calcium buffer within the sarcoplasmic reticulum is [calsequestrin](/source/calsequestrin).,<ref name=":0" /><ref>{{cite journal | vauthors = Briston SJ, Dibb KM, Solaro RJ, Eisner DA, Trafford AW | title = Balanced changes in Ca buffering by SERCA and troponin contribute to Ca handling during β-adrenergic stimulation in cardiac myocytes | journal = Cardiovascular Research | volume = 104 | issue = 2 | pages = 347–54 | date = November 2014 | pmid = 25183792 | pmc = 4240166 | doi = 10.1093/cvr/cvu201 }}</ref>  The effects of calcium buffers depends on their affinity for calcium, as well as the speed with which they bind and release it.<ref>{{Cite journal |last1=Eisner |first1=David |last2=Neher |first2=Erwin |last3=Taschenberger |first3=Holger |last4=Smith |first4=Godfrey |date=2023-06-16 |title=Physiology of intracellular calcium buffering |journal=Physiological Reviews |volume=103 |issue=4 |pages=2767–2845 |doi=10.1152/physrev.00042.2022 |issn=1522-1210 |pmid=37326298|s2cid=259174431 |doi-access=free |pmc=11550887 }}</ref>

== Clinical significance ==
Alterations in calcium buffering within the cytosol have been implicated in the tendency to [arrhythmias](/source/Heart_arrhythmia) (abnormal cardiac rhythms) in some genetic mutations known to cause [hypertrophic cardiomyopathy](/source/hypertrophic_cardiomyopathy).<ref>{{cite journal | vauthors = Schober T, Huke S, Venkataraman R, Gryshchenko O, Kryshtal D, Hwang HS, Baudenbacher FJ, Knollmann BC | title = Myofilament Ca sensitization increases cytosolic Ca binding affinity, alters intracellular Ca homeostasis, and causes pause-dependent Ca-triggered arrhythmia | journal = Circulation Research | volume = 111 | issue = 2 | pages = 170–9 | date = July 2012 | pmid = 22647877 | pmc = 3393041 | doi = 10.1161/CIRCRESAHA.112.270041 }}</ref> Genetic mutations affecting [calsequestrin](/source/calsequestrin) are responsible for an [autosomal recessive](/source/Dominance_(genetics)) form of [catecholaminergic polymorphic ventricular tachycardia](/source/catecholaminergic_polymorphic_ventricular_tachycardia), an inherited cardiac condition that can lead to sudden death.<ref>{{cite journal | vauthors = Lieve KV, van der Werf C, Wilde AA | title = Catecholaminergic Polymorphic Ventricular Tachycardia | journal = Circulation Journal | volume = 80 | issue = 6 | pages = 1285–91 | date = May 2016 | pmid = 27180891 | doi = 10.1253/circj.CJ-16-0326 | doi-access = free }}</ref>  Calcium buffering within atrial myocytes is affected by ageing in large animal models, elevating sarcoplasmic reticulum calcium content, which could potentially contribute towards a tendency to [atrial fibrillation](/source/atrial_fibrillation).<ref>{{cite journal | vauthors = Clarke JD, Caldwell JL, Pearman CM, Eisner DA, Trafford AW, Dibb KM | title = 2+ handling in old sheep atrial myocytes | journal = The Journal of Physiology | volume = 595 | issue = 19 | pages = 6263–6279 | date = October 2017 | pmid = 28752958 | pmc = 5621500 | doi = 10.1113/JP274053 }}</ref>

== See also==

* [Calcium channel](/source/Calcium_channel)
* [Cellular communication (biology)](/source/Cellular_communication_(biology))
* [Excitation contraction coupling](/source/Excitation_contraction_coupling)
* [Protein dynamics](/source/Protein_domain)

== References ==
{{Reflist}}

Category:Calcium signaling

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Adapted from the Wikipedia article [Calcium buffering](https://en.wikipedia.org/wiki/Calcium_buffering) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/Calcium_buffering?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.
