Mediates the electrogenic exchange of Ca(2+) against Na(+) ions across the cell membrane, and thereby contributes to the regulation of cytoplasmic Ca(2+) levels and Ca(2+)-dependent cellular processes (PubMed:8798769, PubMed:9486131). Contributes to cellular Ca(2+) homeostasis in excitable cells, both in muscle and in brain. In a first phase, voltage-gated channels mediate the rapid increase of cytoplasmic Ca(2+) levels due to release of Ca(2+) stores from the endoplasmic reticulum. SLC8A3 mediates the export of Ca(2+) from the cell during the next phase, so that cytoplasmic Ca(2+) levels rapidly return to baseline. Contributes to Ca(2+) transport during excitation-contraction coupling in muscle. In neurons, contributes to the rapid decrease of cytoplasmic Ca(2+) levels back to baseline after neuronal activation, and thereby contributes to modulate synaptic plasticity, learning and memory. Required for normal oligodendrocyte differentiation and for normal myelination. Mediates Ca(2+) efflux from mitochondria and contributes to mitochondrial Ca(2+) ion homeostasis. Ca(2+)(in) + 3 Na(+)(out) = Ca(2+)(out) + 3 Na(+)(in) Calcium transport is down-regulated by Na(+) and stimulated by Ca(2+). Interacts with AKAP1. Detected at neuromuscular junctions. Detected in neurons in brain cortex and hippocampus. Detected in pyramidal cell bodies and processes, in granule cells and interneurons in the CA1 and CA3 region of the hippocampus. Detected on astrocyte processes in brain cortex. Detected on endothelial cells in hippocampus capillaries (at protein level) (PubMed:16914199). Restricted to brain and skeletal muscle (PubMed:8798769). Up-regulated during in vitro differentiation of oligodendrocytes (at protein level). The cytoplasmic Calx-beta domains bind the regulatory Ca(2+). The first Calx-beta domain can bind up to four Ca(2+) ions. The second domain can bind another two Ca(2+) ions that are essential for calcium-regulated ion exchange. Belongs to the Ca(2+):cation antiporter (CaCA) (TC 2.A.19) family. SLC8 subfamily.