title: SLO2 Channels Are Inhibited by All Divalent Cations That Activate SLO1 K+ Channels.
abstract: Two members of the family of high conductance K(+)channels SLO1 and SLO2 are both activated by intracellular cations. However, SLO1 is activated by Ca(2+)and other divalent cations, while SLO2 (Slack or SLO2.2 from rat) is activated by Na(+) Curiously though, we found that SLO2.2 is inhibited by all divalent cations that activate SLO1, with Zn(2+)being the most effective inhibitor with an IC50of ∼8 μmin contrast to Mg(2+), the least effective, with an IC50of ∼ 1.5 mm Our results suggest that divalent cations are not SLO2 pore blockers, but rather inhibit channel activity by an allosteric modification of channel gating. By site-directed mutagenesis we show that a histidine residue (His-347) downstream of S6 reduces inhibition by divalent cations. An analogous His residue present in some CNG channels is an inhibitory cation binding site. To investigate whether inhibition by divalent cations is conserved in an invertebrate SLO2 channel we cloned the SLO2 channel fromDrosophila(dSLO2) and compared its properties to those of rat SLO2.2. We found that, like rat SLO2.2, dSLO2 was also activated by Na(+)and inhibited by divalent cations. Inhibition of SLO2 channels in mammals andDrosophilaby divalent cations that have second messenger functions may reflect the physiological regulation of these channels by one or more of these ions.
authors.affiliation: From the Departments of Neuroscience and National Center for Behavioral Genomics and Volen Center for Complex Systems, Department of Biology, Brandeis University, Waltham, Massachusetts 02458.
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Budelli
authors.affiliation: From the Departments of Neuroscience and.
authors.forename: Qi
authors.initials: Q
authors.lastname: Sun
authors.affiliation: From the Departments of Neuroscience and.
authors.forename: Juan
authors.initials: J
authors.lastname: Ferreira
authors.affiliation: From the Departments of Neuroscience and.
authors.forename: Alice
authors.initials: A
authors.lastname: Butler
authors.affiliation: From the Departments of Neuroscience and.
authors.forename: Celia M
authors.initials: CM
authors.lastname: Santi
authors.affiliation: From the Departments of Neuroscience and Department of Genetics, Washington University School of Medicine, Saint Louis, Missouri 63110 and salkoffl@wustl.edu.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Salkoff
mesh_terms: D000818:Animals; D002413:Cations, Divalent / Q000494:pharmacology*; D029721:Drosophila Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D008274:Magnesium / Q000494:pharmacology*; D051381:Rats; D013045:Species Specificity; D014982:Xenopus laevis; D015032:Zinc / Q000494:pharmacology*
chemical_list: D002413:Cations, Divalent; D029721:Drosophila Proteins; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D008274:Magnesium; D015032:Zinc
keywords: BK channel; Drosophila; SLO1; SLO2; divalent ion; ion channel; kcnt1; neuron; potassium channel; sodium channel
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