Voltage-gated Na+ channel beta 1 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 alpha and beta subunits. Although alpha subunits alone are sufficient to encode functional channels, beta 1 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 beta 1 subunit from human heart and skeletal muscle. The deduced amino acid sequence of the human beta 1 subunit exhibits 96% identity with the rat brain beta 1 subunit. Human beta 1 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 beta 1 subunit that is expressed 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 rapidly. In contrast, the human beta 1 subunit has no effect on the function of the tetrodotoxin-insensitive human heart Na+ channel (hH1). These findings indicate that the human beta 1 subunit is widely expressed but does not functionally modify all Na+ channel isoforms.
Makita
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N
Department of Medicine, Vanderbilt University Medical School, Nashville, Tennessee 37232-2372.
Bennett
P B
PB
George
A L
AL
D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism*; D002888:Chromosomes, Human, Pair 19; D018076:DNA, Complementary / Q000302:isolation & purification; D006801:Humans; D015640:Ion Channel Gating; D008969:Molecular Sequence Data; D009132:Muscles / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D015222:Sodium Channels / Q000235:genetics*; D014981:Xenopus
D018076:DNA, Complementary; D012333:RNA, Messenger; D015222:Sodium Channels