Aquaporin ion conductance properties defined by membrane environment, protein structure, and cell physiology

Sam W. Henderson, Saeed Nourmohammadi, Sunita A. Ramesh, Andrea J. Yool

Research output: Contribution to journalReview articlepeer-review

12 Citations (Scopus)


Aquaporins (AQPs) are multifunctional transmembrane channel proteins permeable to water and an expanding array of solutes. AQP-mediated ion channel activity was first observed when purified AQP0 from bovine lens was incorporated into lipid bilayers. Electrophysiological properties of ion-conducting AQPs since discovered in plants, invertebrates, and mammals have been assessed using native, reconstituted, and heterologously expressed channels. Accumulating evidence is defining amino acid residues that govern differential solute permeability through intrasubunit and central pores of AQP tetramers. Rings of charged and hydrophobic residues around pores influence AQP selectivity, and are candidates for further work to define motifs that distinguish ion conduction capability, versus strict water and glycerol permeability. Similarities between AQP ion channels thus far include large single channel conductances and long open times, but differences in ionic selectivity, permeability to divalent cations, and mechanisms of gating (e.g., by voltage, pH, and cyclic nucleotides) are unique to subtypes. Effects of lipid environments in modulating parameters such as single channel amplitude could explain in part the variations in AQP ion channel properties observed across preparations. Physiological roles of the ion-conducting AQP classes span diverse processes including regulation of cell motility, organellar pH, neural development, signaling, and nutrient acquisition. Advances in computational methods can generate testable predictions of AQP structure–function relationships, which combined with innovative high-throughput assays could revolutionize the field in defining essential properties of ion-conducting AQPs, discovering new AQP ion channels, and understanding the effects of AQP interactions with proteins, signaling cascades, and membrane lipids.

Original languageEnglish
Pages (from-to)181-198
Number of pages18
JournalBiophysical Reviews
Issue number1
Early online date11 Jan 2022
Publication statusPublished - Feb 2022


  • Aquaporin
  • Ion channel
  • Membrane
  • Patch clamp
  • Phospholipid bilayer
  • Protein structure


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