Sequence of the voltage - gated sodium channel b - subunit in wild - type 1 and in qui Õ ering mice
نویسندگان
چکیده
SCN1B, the human gene encoding the b -subunit of the voltage-gated sodium channel has previously been cloned and mapped to Chr 1 19q13.1. The sequence of the homologous mouse gene, Scn1b, has now been determined from cDNA. The mouse gene is highly conserved, encoding a predicted protein with 99%, 98% and 96% amino acid identity to the rat, rabbit, and human homologs, respectively. DNA sequence conservation is also striking in the 3 untranslated region which shows 67% and 98% to human and rat, respectively. Unlike the human and rat homologs, high expression of mRNA from the mouse gene is confined to adult skeletal muscle Ž . and brain, and is not observed in heart. As Scn1b maps to Chr 7, in close genetic proximity to the quiÕering gene qÕ , the coding region of Scn1b was also cloned from a qÕ rqÕ J homozygous mouse and assessed as a candidate for the site of this genetic defect. Comparison of qÕ and wild-type cDNAs showed no changes in the predicted amino acid sequence that could cause the qÕ phenotype. However, three silent polymorphisms in the DNA coding region indicate that Scn1b is close to qÕ, and is within a region of genetic identity with DBAr2J, the inbred background on which the qÕ J allele arose.
منابع مشابه
Voltage-Gated Sodium Channels Modulation by Bothutous Schach Scorpion Venom
Buthotus schach is one of the dangers scorpion in Iran that belong to the Buthidae family. Toxins are existing in venom scorpion, modulate the ion channels by blocking or opening the pore of the channel or by altering the voltage gating and useful as pharmacological tools. In the present study, we investigated the effect of venom and its obtained fractions by gel filtrations on electrophysiolog...
متن کاملReduced sodium channel Na(v)1.1 levels in BACE1-null mice.
The Alzheimer BACE1 enzyme cleaves numerous substrates, with largely unknown physiological consequences. We have previously identified the contribution of elevated BACE1 activity to voltage-gated sodium channel Na(v)1.1 density and neuronal function. Here, we analyzed physiological changes in sodium channel metabolism in BACE1-null mice. Mechanistically, we first confirmed that endogenous BACE1...
متن کاملThe β1-Subunit of Nav1.5 Cardiac Sodium Channel Is Required for a Dominant Negative Effect through α-α Interaction
Brugada syndrome (BrS) is an inherited autosomal dominant cardiac channelopathy. Several mutations on the cardiac sodium channel Na(v)1.5 which are responsible for BrS lead to misfolded proteins that do not traffic properly to the plasma membrane. In order to mimic patient heterozygosity, a trafficking defective mutant, R1432G was co-expressed with Wild Type (WT) Na(v)1.5 channels in HEK293T ce...
متن کاملAn Isoform of Nedd4-2 Plays a Pivotal Role in Electrophysiological Cardiac Abnormalities
We have previously shown that neural precursor cell-expressed developmentally downregulated gene 4-2 (Nedd4-2) isoforms with a C2 domain are closely related to ubiquitination of epithelial sodium channel (ENaC), resulting in salt-sensitive hypertension by Nedd4-2 C2 targeting in mice. The sodium voltage-gated channel alpha subunit 5 (SCN5A) gene encodes the α subunit of the human cardiac voltag...
متن کاملIdentification of Navβ1 Residues Involved in the Modulation of the Sodium Channel Nav1.4
Voltage-gated sodium channels (VGSCs) are heteromeric protein complexes that initiate action potentials in excitable cells. The voltage-gated sodium channel accessory subunit, Navβ1, allosterically modulates the α subunit pore structure upon binding. To date, the molecular determinants of the interface remain unknown. We made use of sequence, knowledge and structure-based methods to identify re...
متن کامل