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J. Biol. Chem., Vol. 269, Issue 48, 30125-30131, Dec, 1994
A Felipe, TJ Knittle, KL Doyle and MM Tamkun
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.
Primary structure and differential expression during development and pregnancy of a novel voltage-gated sodium channel in the mouse
Department of Molecular Physiology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
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