VOLTAGE-GATED NA-RNA EXPRESSED IN ADULT HUMAN SKELETAL-MUSCLE, HEART,AND BRAIN IS ENCODED BY A SINGLE-GENE( CHANNEL BETA(1) SUBUNIT MESSENGER)

Voltage-gated Na+ channels are heteromeric proteins consisting of alph a and beta subunits. Although alpha subunits alone are sufficient to e ncode functional channels, beta(1) subunits appear to modulate the kin etics of inactivation. We have used a cross-species reverse transcript ase polymerase chain reaction approach to isolate cDNAs encoding a Na channel beta(1) subunit from human heart and skeletal muscle. The ded uced amino acid sequence of the human beta(1) subunit exhibits 96% ide ntity with the rat brain beta(1) subunit. Human beta(1) mRNA transcrip ts are abundantly expressed in skeletal muscle, heart, and brain. Geno mic Southern blot hybridization experiments suggest that a single gene located on chromosome 19 encodes the human beta(1) subunit that is ex pressed in all three of these tissues. Co-expression of the human beta (1) subunit with the recombinant human skeletal muscle alpha subunit ( hSkM1) in Xenopus oocytes results in Na+ currents that inactivate rapi dly. In contrast, the human beta(1) subunit has no effect on the funct ion of the tetrodotoxin-insensitive human heart Na+ channel (hH1). The se findings indicate that the human beta(1) subunit is widely expresse d but does not functionally modify all Na+ channel isoforms.