Expression of Sodium-Calcium Exchanger Genes in Heart and Skeletal Muscle Development. Evidence for a Role of Adjacent Cells in Regulation of Transcription and Splicing

Sodium-calcium exchangers (NCX) are universal plasmalemma proteins regulating intracellular calcium concentration in animal tissues. While gene structure and regulation of the cardiac-specific isoform NCX1 are known in considerable detail, no data are available on the effect of extrinsic and/or extrinsic factors that govern tissue-specific transcription of all three isoforms (NCX1-NCX3) as well as their still hypothetical alternative splicing. We studied NCX gene expression in cardiac and skeletal muscles and in brain during rat development, as well as their expression in muscle cells grown in presence of neuron-conditioned medium. Our data demonstrate that NCX1 and NCX3 expression in cardiac and skeletal muscle is coordinately regulated and is sensitive to as yet unidentified factors apparently produced by the neighboring cells. Correct splicing of NCX3 transcript is rapidly disrupted within minutes of tissue dissection, consequently most of the previously reported splicing variants featuring exon skipping appear to be artefactual.