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 β₁ 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 β₁ subunit ORFs are expressed in adult rat brain, skeletal muscle and heart. Heterologous co-expression of β₁ with brain (RIIA) and skeletal muscle (μ1) α 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 β₁ subunit showed a single locus (Scn1b) in mouse chromosome 71.8 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 β₁ subunit forming functional complexes with multiple Na channel isoforms could underlie these deficits.