Cell volume changes regulate slick (Slo2.1), but not slack (Slo2.2) K+ channels

PLoS One. 2014 Oct 27;9(10):e110833. doi: 10.1371/journal.pone.0110833. eCollection 2014.


Slick (Slo2.1) and Slack (Slo2.2) channels belong to the family of high-conductance K+ channels and have been found widely distributed in the CNS. Both channels are activated by Na+ and Cl- and, in addition, Slick channels are regulated by ATP. Therefore, the roles of these channels in regulation of cell excitability as well as ion transport processes, like regulation of cell volume, have been hypothesized. It is the aim of this work to evaluate the sensitivity of Slick and Slack channels to small, fast changes in cell volume and to explore mechanisms, which may explain this type of regulation. For this purpose Slick and Slack channels were co-expressed with aquaporin 1 in Xenopus laevis oocytes and cell volume changes of around 5% were induced by exposure to hypotonic or hypertonic media. Whole-cell currents were measured by two electrode voltage clamp. Our results show that Slick channels are dramatically stimulated (196% of control) by cell swelling and inhibited (57% of control) by a decrease in cell volume. In contrast, Slack channels are totally insensitive to similar cell volume changes. The mechanism underlining the strong volume sensitivity of Slick channels needs to be further explored, however we were able to show that it does not depend on an intact actin cytoskeleton, ATP release or vesicle fusion. In conclusion, Slick channels, in contrast to the similar Slack channels, are the only high-conductance K+ channels strongly sensitive to small changes in cell volume.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Size*
  • Gene Expression
  • Humans
  • Kinetics
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Oocytes / metabolism
  • Potassium Channels / genetics
  • Potassium Channels / metabolism*
  • Potassium Channels, Sodium-Activated
  • Rats
  • Xenopus laevis


  • KCNT1 protein, human
  • KCNT2 protein, human
  • Kcnt2 potassium channel, rat
  • Nerve Tissue Proteins
  • Potassium Channels
  • Potassium Channels, Sodium-Activated
  • kcnt1 protein, rat

Grant support

The work was supported by grants from the Danish Medical Research Council (Grant 0602-00021B), the Novonordisk Foundation, The Lundbeck Foundation (Lucens), The Fouger_Hartmann Foundation and Danish National Foundation for Advanced Technology. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.