title: Cell volume changes regulate slick (Slo2.1), but not slack (Slo2.2) K+ channels.
abstract: 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.
authors.affiliation: Department of Physiology and Biochemistry (IKVH), Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Copenhagen, Denmark.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Tejada
authors.affiliation: Department of Physiology and Biochemistry (IKVH), Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Copenhagen, Denmark.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Stople
authors.affiliation: Department of Physiology and Biochemistry (IKVH), Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Copenhagen, Denmark; Department of Biology, Faculty of Science, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Sofia
authors.initials: S
authors.lastname: Hammami Bomholtz
authors.affiliation: Department of Biology, Faculty of Science, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Anne-Kristine
authors.initials: AK
authors.lastname: Meinild
authors.affiliation: Department of Physiology and Biochemistry (IKVH), Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Copenhagen, Denmark.
authors.forename: Asser Nyander
authors.initials: AN
authors.lastname: Poulsen
authors.affiliation: Department of Physiology and Biochemistry (IKVH), Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Copenhagen, Denmark.
authors.forename: Dan A
authors.initials: DA
authors.lastname: Klaerke
mesh_terms: D000818:Animals; D048429:Cell Size; D015870:Gene Expression; D006801:Humans; D007700:Kinetics; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009865:Oocytes / Q000378:metabolism; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism*; D000081033:Potassium Channels, Sodium-Activated; D051381:Rats; D014982:Xenopus laevis
chemical_list: C585122:KCNT1 protein, human; C480494:KCNT2 protein, human; C480493:Kcnt2 potassium channel, rat; D009419:Nerve Tissue Proteins; D015221:Potassium Channels; D000081033:Potassium Channels, Sodium-Activated; C000626167:kcnt1 protein, rat