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Abstract: The study of bacterial voltage-gated Na+-channels (BacNavs) has provided critical insight into the structural understanding of neuronal Na+ channels in humans. However, virtually nothing is known about the biological function of these channels in bacteria. Here we use an interdisciplinary approach, including electrophysiology and structure prediction, to identify the cytoplasmic C-terminus of BacNav channels as a regulatory domain specific to bacteria and show that it could have a general role in sensing environmental factors relevant to individual bacterial species. While previous work has shown that unfolding of a meta-stable region, between the pore and the C-terminal coiled coil, contributes to temperature-sensitivity, we show that this regulation is extremely sensitive to constraints imposed by the C-terminal coiled coil itself. Although single-residue mismatches between the coiled coil heptad register and the meta-stable region suppress temperature-sensitivity, other non-mismatched coiled coil sequences also caused profound alterations in temperature- and voltage-dependent channel activation, as well as on the conformation of the meta-stable region. In addition to these mechanistic studies, we have mined existing databases to find 825 BacNav channel sequences from diverse bacterial families, environments, and physiologies. Nearly 20% of these were not modeled in AFDB, and investigating their sequence and structural similarity within the evolutionarily divergent C-terminal region provides clues to its functional relevance. Together, our findings show that small changes in coiled coil conformation, which could also result from the interaction with environmental factors, strongly influence the conformation of the entire C-terminus and the voltage- and temperature-sensitivity of BacNav channels.