Molecular and functional characterization of a novel sodium channel TipE-like auxiliary subunit from the American cockroach Periplaneta americana

摘要

In Drosophila melanogaster, the functions of voltage-gated sodium (Na-v) channels are modulated by TipE and its orthologs. Here, we describe a novel TipE homolog of the American cockroach, Periplaneta americana, called PaTipE. Like DmTipE, PaTipE mRNAs are ubiquitously expressed. Surprisingly, PaTipE mRNA was undetectable in neurosecretory cells identified as dorsal unpaired median neurons. Phylogenetic analysis placed this new sequence in TipE clade, indicating an independent evolution from a common ancestor. Contrary to previous reports, our data indicate that the auxiliary subunits of insect Na-v, channels are very distant from the mammalian BKCa auxiliary subunits. To decipher the functional roles of PaTipE, we characterized the gating properties of DmNa(v)1-1 channels co-expressed with DmTipE or PaTipE, in Xenopus oocytes. Compared to DmTipE, PaTipE increased Na+ currents by a 4.2-fold. The voltage-dependence of steady-state fast inactivation of DmNa(v)1-1/PaTipE channels was shifted by 5.8 mV to more negative potentials than that of DmNa(v)1-1/DmTipE channels. DmNa(v)1-1/PaTipE channels recovered 3.2-fold slower from the fast-inactivated state than DmNa(v)1-1/DmTipE channels. In conclusion, this study supports that the insect Na, auxiliary subunits share functional features with their mammalian counterparts, although structurally and phylogenetically distant. (C) 2015 Elsevier Ltd. All rights reserved.