Exporting calcium from cells

• Published in: Cell calcium (Edinburgh) Vol. 38; no. 3; pp. 281 - 289
• Main Authors: Guerini, Danilo, Coletto, Luisa, Carafoli, Ernesto
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier India Pvt Ltd 01-09-2005
• Subjects: Animals; Biological Transport, Active - physiology; Calcium - chemistry; Calcium - metabolism; Calcium Channels - chemistry; Calcium Channels - physiology; Cell Membrane - chemistry; Cell Membrane - metabolism; Humans
• ISSN: 0143-4160; 1532-1991
• DOI: 10.1016/j.ceca.2005.06.032

All eukaryotic cells import Ca
2+ through a number of variously gated plasma membrane channels. Once inside cells, Ca
2+ transmits information to a large number of (enzyme) targets. Eventually, it must be exported again, to prevent the overloading of the cytosol with Ca
2+. Two systems export Ca
2+ from cells: a high affinity, low capacity Ca
2+-ATPase, and a lower affinity, but much larger capacity, Na
+/Ca
2+ exchanger. The ATPase (commonly called the Ca
2+ pump) is the fine-tuner of cell Ca
2+, as it functions well even if the concentration of the ion drops below the μM level. It is a large enzyme, with 10 transmembrane domains and a C-terminal cytosolic tail that contains regulatory sites, including a calmodulin-binding domain. Four distinct gene products plus a large number of splice variants have been described. Some are tissue specific, the isoform 2 being specifically expressed in the sensorial cells of the Corti organ in the inner-ear. Its genetic absence causes deafness in mice. Two different families of the Na
+/Ca
2+ exchanger exist, one of which, originally described in photoreceptors, transports K
+ and Ca
2+ in exchange for Na
+. The exchanger is particularly active in excitable cells, e.g., heart, where the necessity cyclically arises to rapidly eject large amounts of Ca
2+. In addition to heart, the exchanger is particularly important to neurons: the cleavage of the most important neuronal isoform (NCX3) by calpains activated by excitotoxic treatments generates Ca
2+ overload and eventually cell death.