Primary structure and differential expression during development and pregnancy of a novel voltage-gated sodium channel in the mouse.

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.