The molecular nature of the canine cardiac sarcolemmal Na(+)-Ca2+ exchanger has been investigated by purification of the protein and by sequencing and expression of an exchanger cDNA clone. The mature exchanger protein is apparently 120 kDa, with glycosylation at a single asparagine residue near the amino terminus. A proposed model for the exchanger protein includes 11 transmembrane segments, a large cytoplasmic domain that is not involved in ion translocation, an exchanger inhibitory site, two Ca2+ interaction sites and an ion-translocation pathway. Experiments are now under way to test the proposed model.