Molecular cloning and functional expression of the human sodium channel beta(1B) subunit, a novel splicing variant of the beta(1) subunit

The voltage gated sodium channel comprises a pore-forming alpha subunit and regulatory beta subunits. We report here the identification and characterization of a novel splicing variant of the human beta(1) subunit, termed beta(1B). The 807 bp open reading frame of the human beta(1B) subunit encodes a 268 residue protein with a calculated molecular mass of 30.4 kDa. The novel human beta(1B) subunit shares an identical N-terminal half (residues 1-149) with the human beta(1) subunit, but contains a novel C-terminal half (residues 150-268) of less than 17% sequence identity with the human beta(1) subunit. The C-terminal region of the human beta(1B) is also significantly different from that of the rat beta(1A) subunit, sharing less than 33% sequence identity. Tissue distribution studies reveal that the human beta(1B) subunit is expressed predominantly in human brain, spinal cord, dorsal root ganglion and skeletal muscle. Functional studies in oocytes demonstrate that the human beta(1B) subunit increases the ionic current when coexpressed with the tetrodotoxin sensitive channel, Na(V)1.2, without significantly changing voltage dependent kinetics and steady-state properties, thus distinguishing it from the human beta(1) and rat beta(1A) subunits.