A single B1 subunit mapped to mouse chromosome 7 may be a common component of Na channel isoforms from brain, skeletal muscle and heart.
A beta 1 subunit associated with one or more isoforms of brain voltage-sensitive Na channels has previously been cloned, sequenced and expressed. Northern and Western blot analyses have suggested that homologues to this protein are expressed in skeletal muscle and heart. Here, reverse transcriptase-polymerase chain reaction (RT-PCR)/cloning reveals that transcripts encoding identical beta 1 subunit ORFs are expressed in adult rat brain, skeletal muscle and heart. Heterologous co-expression of beta 1 with brain (RIIA) and skeletal muscle (mu 1) alpha subunits caused a stabilization of normal, rapidly inactivating (mode 1) gating relative to anomalous, non-inactivating (mode 2) states and a negative shift in steady state inactivation. Chromosome mapping of the beta 1 subunit showed a single locus (Scn1b) in mouse chromosome 7 1.8 cM (+/- 1.2 cM) distal to D19F11S1h and 0.9 cM (+/- 0.9 cM) proximal to Pkca. This locus is in the region of the mouse mutant "quivering," characterized by a variety of neurological disorders and muscle paralysis. A mutation in a single beta 1 subunit forming functional complexes with multiple Na channel isoforms could underlie these deficits.
Tong
J
J
Dept. of Physiology, Johns Hopkins University School of Medicine.
Potts
J F
JF
Rochelle
J M
JM
Seldin
M F
MF
Agnew
W S
WS
D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism*; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D007700:Kinetics; D046911:Macromolecular Substances; D008564:Membrane Potentials; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice / Q000235:genetics*; D008818:Mice, Neurologic Mutants / Q000235:genetics; D008969:Molecular Sequence Data; D009115:Muridae / Q000235:genetics*; D009132:Muscles / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D009838:Oligodeoxyribonucleotides; D009865:Oocytes / Q000502:physiology; D016366:Open Reading Frames; D009928:Organ Specificity; D016133:Polymerase Chain Reaction; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D051381:Rats / Q000235:genetics; D015222:Sodium Channels / Q000378:metabolism*; D014981:Xenopus
D046911:Macromolecular Substances; D008565:Membrane Proteins; D009838:Oligodeoxyribonucleotides; D015222:Sodium Channels; D012313:RNA