Felipe A, Knittle T J, Doyle K L, Tamkun M M
Department of Molecular Physiology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
J Biol Chem. 1994 Dec 2;269(48):30125-31.
Until recently, all cloned vertebrate voltage-dependent sodium channels exhibited high sequence homology to one another and appeared to comprise a single multigene subfamily. An exception is the human Nav2.1 channel proposed to represent a second Na+ channel (NaCh) gene subfamily since comparison with previously cloned voltage-gated NaChs revealed only 40-45% identity. We have now cloned a mouse NaCh (mNav2.3) from an atrial tumor cell line that shows high amino acid sequence identity to hNav2.1 in functionally relevant regions such as the pore-forming segments, S4 segments, and inactivation gate sequence. Overall sequence identity is 68%. mNav2.3 mRNA was most abundant in heart and uterus, and the transcript levels in heart, brain, and skeletal muscle were differentially regulated during development. Transcript levels in heart were greatest immediately after birth. mNav2.3 transcript levels in pregnant uterus increased 3-fold between day 15 of pregnancy and birth and then declined 15-fold during the 2 days following delivery. The mNav2.3 amino acid sequence indicates that the Nav2 NaCh gene subfamily is well conserved across species, and the tissue-specific and developmental regulation of mRNA expression suggests these channels play important physiological roles in cardiac and uterine muscle.
直到最近，所有克隆的脊椎动物电压依赖性钠通道彼此之间都表现出高度的序列同源性，并且似乎构成了一个单一的多基因亚家族。一个例外是人类Nav2.1通道，由于与先前克隆的电压门控钠通道相比，其同一性仅为40%-45%，因此被认为代表第二个钠通道（NaCh）基因亚家族。我们现在从一个心房肿瘤细胞系中克隆了一种小鼠钠通道（mNav2.3），它在功能相关区域，如孔形成段、S4段和失活门序列，与hNav2.1显示出高氨基酸序列同一性。总体序列同一性为68%。mNav2.3 mRNA在心脏和子宫中最为丰富，并且在发育过程中，心脏、大脑和骨骼肌中的转录水平受到差异调节。出生后立即，心脏中的转录水平最高。怀孕子宫中mNav2.3转录水平在妊娠第15天到出生之间增加了3倍，然后在分娩后的2天内下降了15倍。mNav2.3氨基酸序列表明，Nav2钠通道基因亚家族在物种间具有良好的保守性，mRNA表达的组织特异性和发育调节表明这些通道在心肌和子宫肌中发挥重要的生理作用。
