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Evolution of voltage-gated Na⁺ channels

Alan L. Goldin^*

Department of Microbiology and Molecular Genetics, University of California, Irvine, CA 92697-4025, USA

View larger version (23K): [in a new window]   Fig. 1. A schematic diagram of the voltage-gated Na+ channel subunit. The four homologous domains are labeled I–IV, and the six transmembrane segments in each domain are labeled S1–S6. The critical motif of the fast inactivation particle (IFM) is shown on the cytoplasmic linker connecting domains III and IV. The channel is aligned with the extracellular side of the membrane on the top. The lengths that are shown for the N and C termini and the interdomain cytoplasmic loops are consistent with the sequence of the Nav1.2 mammalian Na+ channel, but these linkers (except for that between domains III and IV) vary greatly in length and sequence among the different Na+ channel isoforms. P, P loop.

View larger version (20K): [in a new window]   Fig. 2. This proposed phylogenetic tree for the voltage-gated Na+ channel subunits was generated using sequences of the channels listed in Tables 1 and 2. The mammalian channels are in blue, the non-mammalian vertebrate channels are in green and the invertebrate channels are in red. This unrooted tree represents the optimal tree based on parsimony analysis of nucleotide sequences. To perform the analysis, the amino acid sequences for all the isoforms were aligned using Clustal W (Thompson et al., 1994). The amino acid sequences in the alignments were then replaced with the published nucleotide sequences, and the nucleotide sequence alignments were subjected to analysis using the program PAUP* (Swofford, 1998). Divergent portions, including most of the terminal regions and the cytoplasmic loops between domains I and II and domains II and III, were excluded from the PAUP* analysis. The numbers at the nodes indicate the bootstrap values for 100 replications. When a number is not indicated, the bootstrap value was less than 50. The scale bar represents 500 substitutions. Channels and species are identified in Tables 1 and 2.

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