title: SLO-2 isoforms with unique Ca(2+) - and voltage-dependence characteristics confer sensitivity to hypoxia in C. elegans.
abstract: Slo channels are large conductance K (+) channels that display marked differences in their gating by intracellular ions. Among them, the Slo1 and C. elegans SLO-2 channels are gated by calcium (Ca ( 2+) ), while mammalian Slo2 channels are activated by both sodium (Na (+) ) and chloride (Cl (-) ). Here, we report that SLO-2 channels, SLO-2a and a novel N-terminal variant isoform, SLO-2b, are activated by Ca ( 2+) and voltage, but in contrast to previous reports they do not exhibit Cl (-) sensitivity. Most importantly, SLO-2 provides a unique case in the Slo family for sensing Ca ( 2+) with the high-affinity Ca ( 2+) regulatory site in the RCK1 but not the RCK2 domain, formed through interactions with residues E319 and E487 (that correspond to D362 and E535 of Slo1, respectively). The SLO-2 RCK2 domain lacks the Ca ( 2+) bowl structure and shows minimal Ca ( 2+) dependence. In addition, in contrast to SLO-1, SLO-2 loss-of-function mutants confer resistance to hypoxia in C. elegans. Thus, the C. elegans SLO-2 channels possess unique biophysical and functional properties.
authors.affiliation: Department of Physiology and Biophysics, Virginia Commonwealth University, Medical College of Virginia Campus, Richmond, VA, USA. zzhang5@vcu.edu
authors.forename: Zhe
authors.initials: Z
authors.lastname: Zhang
authors.forename: Qiong-Yao
authors.initials: QY
authors.lastname: Tang
authors.forename: Joseph T
authors.initials: JT
authors.lastname: Alaimo
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Davies
authors.forename: Jill C
authors.initials: JC
authors.lastname: Bettinger
authors.forename: Diomedes E
authors.initials: DE
authors.lastname: Logothetis
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D015220:Calcium Channels; D026901:Membrane Transport Proteins; D020033:Protein Isoforms; C402625:SLO-2 protein, C elegans; D002118:Calcium
keywords: Ca2+ binding; Slo channel; allosteric regulation; ion channels; membrane function; polymerase chain reaction (PCR); protein metal ion interaction