Ionic selectivity and thermal adaptations within the voltage-gated sodium channel family of alkaliphilic Bacillus.
Entry and extrusion of cations are essential processes in living cells. In alkaliphilic prokaryotes, high external pH activates voltage-gated sodium channels (Nav), which allows Na(+) to enter and be used as substrate for cation/proton antiporters responsible for cytoplasmic pH homeostasis. Here, we describe a new member of the prokaryotic voltage-gated Na(+) channel family (NsvBa; <underline>N</underline>on-<underline>s</underline>elective <underline>v</underline>oltage-gated, <underline>B</underline>acillus <underline>a</underline>lcalophilus) that is nonselective among Na(+), Ca(2+) and K(+) ions. Mutations in NsvBa can convert the nonselective filter into one that discriminates for Na(+) or divalent cations. Gain-of-function experiments demonstrate the portability of ion selectivity with filter mutations to other Bacillus Nav channels. Increasing pH and temperature shifts their activation threshold towards their native resting membrane potential. Furthermore, we find drugs that target Bacillus Nav channels also block the growth of the bacteria. This work identifies some of the adaptations to achieve ion discrimination and gating in Bacillus Nav channels.
Department of Cardiology, Howard Hughes Medical Institute, Boston Children's Hospital, Boston, United States.
Paul G
PG
DeCaen
Graduate School of Life Sciences, Toyo University, Gunma, Japan.
Yuka
Y
Takahashi
Department of Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai, New York, United States.
Terry A
TA
Krulwich
Graduate School of Life Sciences, Toyo University, Gunma, Japan.
Masahiro
M
Ito
Department of Cardiology, Howard Hughes Medical Institute, Boston Children's Hospital, Boston, United States.
David E
DE
Clapham
D000220:Adaptation, Biological / Q000187:drug effects*; D000468:Alkalies / Q000494:pharmacology; D000595:Amino Acid Sequence; D001407:Bacillus / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D002412:Cations; D002463:Cell Membrane Permeability; D006863:Hydrogen-Ion Concentration; D008969:Molecular Sequence Data; D009068:Movement / Q000187:drug effects; D005810:Multigene Family; D009154:Mutation / Q000235:genetics; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013696:Temperature; D061566:Voltage-Gated Sodium Channels / Q000737:chemistry / Q000378:metabolism*
D000468:Alkalies; D002412:Cations; D026941:Sodium Channel Blockers; D061566:Voltage-Gated Sodium Channels
antibiotics; bacteria physiology; biochemical adaptations; biophysics; evolution; infectious disease; ion selectivity; microbiology; none; pharmacology; structural biology