Molecular Identities and ATP Release Activities of Two Types of Volume-Regulatory Anion Channels, VSOR and Maxi-Cl

Curr Top Membr. 2018:81:125-176. doi: 10.1016/bs.ctm.2018.07.004. Epub 2018 Aug 17.


An elaborate volume regulation system based on interplay of ion channels and transporters was evolved to cope with constant osmotic challenges caused by intensive metabolism, transport and other physiological/pathophysiological events. In animal cells, two types of anion channels are directly activated by cell swelling and involved in the regulatory volume decrease (RVD): volume-sensitive outwardly rectifying anion channel (VSOR), also called volume-regulated anion channel (VRAC), and Maxi-Cl which is the most major type of maxi-anion channel (MAC). These two channels have very different biophysical profiles and exhibit opposite dependence on intracellular ATP. After several decades of verifying many false-positive candidates for VSOR and Maxi-Cl, LRRC8 family proteins emerged as major VSOR components, and SLCO2A1 protein as a core of Maxi-Cl. Still, neither of these proteins alone can fully reproduce the native channel phenotypes suggesting existence of missing components. Although both VSOR and Maxi-Cl have pores wide enough to accommodate bulky ATP4- and MgATP2- anions, evidence accumulated hitherto, based on pharmacological and gene silencing experiments, suggests that Maxi-Cl, but not VSOR, serves as one of the major pathways for the release of ATP from swollen and ischemic/hypoxic cells. Relations of VSOR and Maxi-Cl with diseases and their selective pharmacology are the topics promoted by recent advance in molecular identification of the two volume-activated, volume-regulatory anion channels.

Keywords: ATP conductance; ATP release; Anion channel; Cell volume regulation; LRRC8; Regulatory volume decrease; SLCO2A1.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adenosine Triphosphate / metabolism*
  • Animals
  • Anions / metabolism*
  • Cell Size*
  • Humans
  • Ion Channels / metabolism*
  • Signal Transduction


  • Anions
  • Ion Channels
  • Adenosine Triphosphate