title: Heteromeric Slick/Slack K+ channels show graded sensitivity to cell volume changes.
abstract: Slick and Slack high-conductance K+ channels are found in the CNS, kidneys, pancreas, among other organs, where they play an important role in cell excitability as well as in ion transport processes. They are both activated by Na+ and Cl- but show a differential regulation by cell volume changes. Slick has been shown to be regulated by cell volume changes, whereas Slack is insensitive. α-subunits of these channels form homomeric as well as heteromeric channels. It is the aim of this work to explore whether the subunit composition of the Slick/Slack heteromeric channel affects the response to osmotic challenges. In order to provide with the adequate water permeability to the cell membrane of Xenopus laevis oocytes, mRNA of aquaporin 1 was co-expressed with homomeric or heteromeric Slick and Slack α-subunits. Oocytes were superfused with hypotonic or hypertonic buffers and changes in currents were measured by two-electrode voltage clamp. This work presents the first heteromeric K+ channel with a characteristic graded sensitivity to small and fast changes in cell volume. Our results show that the cell volume sensitivity of Slick/Slack heteromeric channels is dependent on the number of volume sensitive Slick α-subunits in the tetrameric channels, giving rise to graded cell volume sensitivity. Regulation of the subunit composition of a channel may constitute a novel mechanism to determine volume sensitivity of cells.
authors.affiliation: Department of Physiology, IKVH, Faculty of Health and Medical Sciences, University of Copenhagen, Dyrlaegevej, Frederiksberg C, Denmark.
authors.forename: Maria A
authors.identifier: http://orcid.org/0000-0002-3495-8423
authors.initials: MA
authors.lastname: Tejada
authors.affiliation: Department of Physiology, IKVH, Faculty of Health and Medical Sciences, University of Copenhagen, Dyrlaegevej, Frederiksberg C, Denmark.
authors.forename: Nadia
authors.initials: N
authors.lastname: Hashem
authors.affiliation: Department of Physiology, IKVH, Faculty of Health and Medical Sciences, University of Copenhagen, Dyrlaegevej, Frederiksberg C, Denmark.
authors.forename: Kirstine
authors.initials: K
authors.lastname: Calloe
authors.affiliation: Department of Physiology, IKVH, Faculty of Health and Medical Sciences, University of Copenhagen, Dyrlaegevej, Frederiksberg C, Denmark.
authors.forename: Dan A
authors.initials: DA
authors.lastname: Klaerke
mesh_terms: D000818:Animals; D051398:Aquaporin 1 / Q000378:metabolism; D048429:Cell Size; D006801:Humans; D006982:Hypertonic Solutions / Q000494:pharmacology; D007038:Hypotonic Solutions / Q000494:pharmacology; D008564:Membrane Potentials / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000378:metabolism; D009865:Oocytes; D009994:Osmolar Concentration; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000737:chemistry* / Q000378:metabolism; D000081033:Potassium Channels, Sodium-Activated; D055503:Protein Multimerization; D021122:Protein Subunits; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014982:Xenopus laevis
chemical_list: D006982:Hypertonic Solutions; D007038:Hypotonic Solutions; C480494:KCNT2 protein, human; D009419:Nerve Tissue Proteins; D015221:Potassium Channels; D000081033:Potassium Channels, Sodium-Activated; D021122:Protein Subunits; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; C000626167:kcnt1 protein, rat; D051398:Aquaporin 1