Voltage-gated Na⁺ channel β₁ subunit mRNA expressed in adult human skeletal muscle, heart, and brain is encoded by a single gene

Voltage-gated Na⁺ channels are heteromeric proteins consisting of α and β subunits. Although α subunits alone are sufficient to encode functional channels, β₁ subunits appear to modulate the kinetics of inactivation. We have used a cross-species reverse transcriptase polymerase chain reaction approach to isolate cDNAs encoding a Na⁺ channel β₁ subunit from human heart and skeletal muscle. The deduced amino acid sequence of the human β₁ subunit exhibits 96% identity with the rat brain β₁ subunit. Human β₁ mRNA transcripts are abundantly expressed in skeletal muscle, heart, and brain. Genomic Southern blot hybridization experiments suggest that a single gene located on chromosome 19 encodes the human β₁ subunit that is expressed in all three of these tissues. Co-expression of the human β₁ subunit with the recombinant human skeletal muscle α subunit (hSkM1) in Xenopus oocytes results in Na⁺ currents that inactivate rapidly. In contrast, the human β₁ subunit has no effect on the function of the tetrodotoxin-insensitive human heart Na⁺ channel (hH1). These findings indicate that the human β₁ subunit is widely expressed but does not functionally modify all Na⁺ channel isoforms.