Mediates the exchange of one Ca(2+) ion against three to four Na(+) ions across the cell membrane, and thereby contributes to the regulation of cytoplasmic Ca(2+) levels and Ca(2+)-dependent cellular processes (PubMed:8422940, PubMed:8454039, PubMed:10894800, PubMed:12502557). Contributes to Ca(2+) transport during excitation-contraction coupling in muscle. 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. SLC8A1 mediates the export of Ca(2+) from the cell during the next phase, so that cytoplasmic Ca(2+) levels rapidly return to baseline. Required for normal embryonic heart development and the onset of heart contractions (By similarity). Ca(2+)(in) + 3 Na(+)(out) = Ca(2+)(out) + 3 Na(+)(in) Activated by micromolar levels of Ca(2+) (PubMed:12502557). Only active at low calcium concentrations (PubMed:15040000). Not activated by PKC (PubMed:15040000). Active at all calcium levels tested (PubMed:15040000). Activated by PKC (PubMed:15040000). Only active at low calcium concentrations (PubMed:15040000). Activated by PKC (PubMed:15040000). Detected in heart, brain cortex and hippocampus (at protein level) (PubMed:16914199). Cardiac sarcolemma or brain, and spleen. Expressed in all regions of the kidney, highest levels of expression in the distal convoluted tubule. Expressed throughout the CNS, in decreasing order of abundance in hippocampus, cortex, cerebellum, hypothalamus, midbrain and striatum. Expressed in numerous regions of the brain including multiple cortical layers, hippocampus, septal nuclei, thalamic nuclei, cerebellum, hypothalamus, olfactory bulb and brainstem. Also expressed in various regions of the spinal cord, ventricles and atria of the heart, lung, adrenals and kidney. Isoform 4 seems to be a predominant isoform in aorta, stomach, liver, and kidney. 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.