The weakly electric fish Sternopygus macrurus emits an electric organ discharge (EOD)
composed of a series of pulses. The EOD pulse is mainly shaped by sodium currents.
There are two sodium channel α subunits orthologs of the mammalian Nav1.4 expressed
in the EO of Sternopygus. Previous studies identified a novel splice variant of the
Nav1.4b (Nav1.4bL), in which an extra 51-amino acid occurs in the N terminal end.
Nav1.4bL currents inactivate and recover from inactivation significantly faster than
Nav1.4bS. The voltage-dependence of steady-state inactivation of smNav1.4bL shifts to
hyperpolarized potential. Structural analysis predicts an α-helix in the middle of the
extended N terminus. Removal of a proline right after the α-helix significantly slows
down current decay but has no effect on channel recovery from inactivation, suggesting
inactivation and recovery have independent mechanism. Mutagenesis analysis of the
extended N terminus showed that the short helical region, especially the positive charges
in the helix, is an important determinant for channel voltage-dependence of steady-state
inactivation. However, other residues outside the helical region are required for regulation of fast inactivation and recovery form inactivation. Functional and structural analysis provides evidence for the importance of the C terminus
in fish Nav1.4b channel properties. Chimera in which the C terminus of smNav1.4bS was
substituted by the human Nav1.4 C terminus, shows an 11 mV positive shift in voltage-dependence
of activation and a -16 mV negative shift in inactivation. Deletion of the
distal half of smNav1.4bS negatively shifted voltage-dependence of inactivation and
significantly accelerated channel recovery from inactivation. In the deletion mutant, the
regulation by the N segment is missing. Substitution of the C terminus mutant retains
wild type channel inactivation and recovery properties and can be regulated by N
segment again.
My study provides evidence that the extended N terminus of smNav1.4bL binds the distal
part of C terminal tail to modulate channel inactivation properties. This is the first time to
show the distal C terminus is involved in channel recovery from inactivation. Studies in
the fish sodium channel properties provide useful information to understand function and structure of voltage-gated sodium channels. / text
| Identifer | oai:union.ndltd.org:UTEXAS/oai:repositories.lib.utexas.edu:2152/6626 |
| Date | 22 October 2009 |
| Creators | Wu, Mingming |
| Source Sets | University of Texas |
| Language | English |
| Detected Language | English |
| Format | electronic |
| Rights | Copyright is held by the author. Presentation of this material on the Libraries' web site by University Libraries, The University of Texas at Austin was made possible under a limited license grant from the author who has retained all copyrights in the works. |
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