(A) A diagram depicting the membrane proteins involved in the Na+ cycle of Bacillus alcalophilus. The cation/proton antiporters, including Mrp antiporters, catalyze net proton accumulation in the cytoplasm in cells that are extruding protons during respiration. Na+ re-entry in support of pH homeostasis is achieved by Na+ solute symporters and through the voltage-gated channel, NsvBa . (B) Relatedness within functionally characterized members of the bacterial sodium channel superfamily. A rooted phylogenic tree analysis of bacterial Nav channels calculated by using the CLUSTALW program (http://clustalw.genome.jp). Branch lengths are proportional to the sequence divergence (scale bar = 0.2 substitutions per amino acid site). (C) An alignment of the selectivity filters from various Na+, K+, and nonselective ion channels. The pore region from the indicated ion channel families (italic) were aligned using the ClustalW multiple sequence alignment program applying the default color scheme with <60% conservation of character: Hydrophobic (blue); polar (green); glutamine, glutamate, aspartate (magenta). Special amino acids are designated with their own color: glycine (orange); proline (yellow) and tyrosine or histidine (cyan). The barrels indicate the regions spanning the pore helices found in the Shaker (K+-selective), NaK and NavRh crystal structures.