Na+/Ca2+ Exchanger

Na+/Ca2+ Exchanger

Na+/Ca2+ exchanger (sodium-calcium exchanger , NCX) is an antiporter membrane protein that removes calcium from cells. The Na+/Ca2+ exchanger (NCX) plays in the function and regulation of several cellular activities.

An overview of Na+/Ca2+ Exchanger

Na+/Ca2+ Exchanger (NCX), a bidirectional ion transporter, regulates intracellular Ca2+ concentration in the forward mode or the reverse mode, and is widely expressed in cytoplasmic membrane, mitochondrial membrane, endoplasmic reticulum in various cells. The realization of lots of cellular functions depends on intracellular Ca2+, including differentiation, survival, membrane excitability. The members of NCX family are encoded by SLC8 gene family belonging to the Ca2+/Cation antiporter, and play an essential role in a variety of biological functions, such as immune response and blood pressure. NCX is composed of 970 amino acids and has a molecular weight of 108 kDa, which is characterized by low Ca2+ affinity but high Ca2+ transport rate.

Major types of Na+/Ca2+ Exchanger

There are three types of NCX identified in mammals: NCX1, NCX2, NCX3. NCX1 is mainly expressed in heart, kidney and brain tissues, and is also distributed in other tissues. NCX2 and NCX3 are restricted to brain tissue and skeletal muscle. The three types of NCX containsimilar amino acid sequence and properties.

Inhibition of Na+/Ca2+ Exchanger

Undoubtedly, NCX has become a hot target because clinical studies have suggested the therapeutic potential of NCX inhibitors. In 1996, KB-R7943, an isothiourea derivative, was synthesized as a potent NCX inhibitor, which was used to block the reverse mode of NCX activity. Kazuhiro and his colleagues reported NCX inhibitor with high selectivity and even more potency than KB-R7943, called SEA0400, which could prevent the activity of NCX in both neuronal and cardiac preparations. However, the understanding of molecular and cellular mechanisms of NCX functions is still poor, which may make it difficult to generate a new generation of NCX inhibitors.

Na+/Ca2+ Exchanger and diseases

In recent years, emerging data suggested that NCX could not only regulate intracellular Ca2+ concentration, but also implicated in cell growth and some signaling pathways. Therefore, NCX is involved in several diseases including Parkinson’s disease, arrhythmias, heart failure, and myocardial ischemia–reperfusion injury.


1. Takuma, K., Ago, Y., & Matsuda, T. (2013). The glial sodium-calcium exchanger: a new target for nitric oxide-mediated cellular toxicity.Current Protein and Peptide Science,14(1), 43-50.

2. Khananshvili, D. (2014). Sodium-calcium exchangers (NCX): molecular hallmarks underlying the tissue-specific and systemic functions.Pflügers Archiv-European Journal of Physiology,466(1), 43-60.

3. Ottolia, M., Torres, N., Bridge, J. H., Philipson, K. D., & Goldhaber, J. I. (2013). Na/Ca exchange and contraction of the heart.Journal of molecular and cellular cardiology,61, 28-33.

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