Bacterial voltage-gated sodium channels (BacNa(V)s) from the soil, sea, and salt lakes enlighten molecular mechanisms of electrical signaling and pharmacology in the brain and heart.

Jian Payandeh, Daniel L Minor

Journal: Journal of molecular biology 2015;427(1):3-30

PMID: 25158094

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Abstract

Voltage-gated sodium channels (Na(V)s) provide the initial electrical signal that drives action potential generation in many excitable cells of the brain, heart, and nervous system. For more than 60years, functional studies of Na(V)s have occupied a central place in physiological and biophysical investigation of the molecular basis of excitability. Recently, structural studies of members of a large family of bacterial voltage-gated sodium channels (BacNa(V)s) prevalent in soil, marine, and salt lake environments that bear many of the core features of eukaryotic Na(V)s have reframed ideas for voltage-gated channel function, ion selectivity, and pharmacology. Here, we analyze the recent advances, unanswered questions, and potential of BacNa(V)s as templates for drug development efforts.

Address: Department of Structural Biology, Genentech, Inc., South San Francisco, CA 94080, USA. Electronic address: [email protected].; Cardiovascular Research Institute, Departments of Biochemistry and Biophysics and Cellular and Molecular Pharmacology, California Institute for Quantitative Biomedical Research, University of California, San Francisco, CA 93858-2330, USA; Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. Electronic address: [email protected].

DOI: 10.1016/j.jmb.2014.08.010

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MeSH Terms: Bacteria, Brain, Electric Stimulation, Heart, Lakes, Soil, Voltage-Gated Sodium Channels