Transcripts homologous to the rat brain sodium channel beta subunit (beta 1) are prominently expressed in both innervated and denervated adult skeletal muscle and in heart, but not in neonatal skeletal or cardiac muscle. Regulation of beta 1 mRNA expression closely parallels that of SkM1 alpha during development, after denervation in adult muscle, and in primary muscle culture, but does not follow SkM2 expression under any condition examined. In oocytes, beta 1 interacts functionally with SkM1 to modulate the abnormally slow inactivation kinetics observed with this alpha subunit expressed alone. We conclude that a common beta 1 subunit is expressed in skeletal muscle, heart, and brain and that in skeletal muscle, this subunit is specifically associated with the SkM1, rather than the SkM2, sodium channel isoform.