On the molecular nature of large-pore channels

J Mol Biol. 2021 Aug 20;433(17):166994. doi: 10.1016/j.jmb.2021.166994. Epub 2021 Apr 16.


Membrane transport is a fundamental means to control basic cellular processes such as apoptosis, inflammation, and neurodegeneration and is mediated by a number of transporters, pumps, and channels. Accumulating evidence over the last half century has shown that a type of so-called "large-pore channel" exists in various tissues and organs in gap-junctional and non-gap-junctional forms in order to flow not only ions but also metabolites such as ATP. They are formed by a number of protein families with little or no evolutionary linkages including connexin, innexin, pannexin, leucine-rich repeat-containing 8 (LRRC8), and calcium homeostasis modulator (CALHM). This review summarizes the history and concept of large-pore channels starting from connexin gap junction channels to the more recent developments in innexin, pannexin, LRRC8, and CALHM. We describe structural and functional features of large-pore channels that are crucial for their diverse functions on the basis of available structures.

Keywords: CALHM; Connexin; Innexin; LRRC8; Pannexin.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Biological Transport / physiology
  • Gap Junctions / metabolism
  • Humans
  • Ion Channels / metabolism*
  • Ions / metabolism*


  • Ion Channels
  • Ions