Ion channel chameleons: Switching ion selectivity by alternative splicing

J Biol Chem. 2023 Mar;299(3):102946. doi: 10.1016/j.jbc.2023.102946. Epub 2023 Jan 24.

Abstract

Voltage-gated sodium and calcium channels are distinct, evolutionarily related ion channels that achieve remarkable ion selectivity despite sharing an overall similar structure. Classical studies have shown that ion selectivity is determined by specific binding of ions to the channel pore, enabled by signature amino acid sequences within the selectivity filter (SF). By studying ancestral channels in the pond snail (Lymnaea stagnalis), Guan et al. showed in a recent JBC article that this well-established mechanism can be tuned by alternative splicing, allowing a single CaV3 gene to encode both a Ca2+-permeable and an Na+-permeable channel depending on the cellular context. These findings shed light on mechanisms that tune ion selectivity in physiology and on the evolutionary basis of ion selectivity.

Keywords: CaV3; T-type channels; calcium channels; ion channels; ion selectivity; lymnaea CaV3; sodium channels.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alternative Splicing*
  • Amino Acid Sequence
  • Animals
  • Calcium / metabolism
  • Calcium Channels* / metabolism
  • Ions / metabolism
  • Snails / metabolism
  • Voltage-Gated Sodium Channels* / metabolism

Substances

  • Calcium
  • Calcium Channels
  • Ions
  • Voltage-Gated Sodium Channels