Tong J, Potts J F, Rochelle J M, Seldin M F, Agnew W S
Dept. of Physiology, Johns Hopkins University School of Medicine.
Biochem Biophys Res Commun. 1993 Sep 15;195(2):679-85. doi: 10.1006/bbrc.1993.2099.
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.
先前已克隆、测序并表达了与一种或多种脑电压敏感性钠通道亚型相关的β1亚基。Northern和Western印迹分析表明，该蛋白的同源物在骨骼肌和心脏中表达。在此，逆转录聚合酶链反应（RT-PCR）/克隆显示，编码相同β1亚基开放阅读框（ORF）的转录本在成年大鼠脑、骨骼肌和心脏中表达。β1与脑（RIIA）和骨骼肌（μ1）α亚基的异源共表达导致相对于异常的、非失活的（模式2）状态，正常的、快速失活的（模式1）门控得到稳定，并且稳态失活出现负向偏移。β1亚基的染色体定位显示在小鼠染色体7上有一个单一基因座（Scn1b），位于D19F11S1h远端1.8 cM（±1.2 cM）处，Pkca近端0.9 cM（±0.9 cM）处。该基因座位于小鼠突变体“颤抖”区域，其特征为多种神经疾病和肌肉麻痹。与多种钠通道亚型形成功能复合物的单个β1亚基中的突变可能是这些缺陷的基础。
