The sodium-activated potassium channel is encoded by a member of the Slo gene family.
Na(+)-activated potassium channels (K(Na)) have been identified in cardiomyocytes and neurons where they may provide protection against ischemia. We now report that K(Na) is encoded by the rSlo2 gene (also called Slack), the mammalian ortholog of slo-2 in C. elegans. rSlo2, heterologously expressed, shares many properties of native K(Na) including activation by intracellular Na(+), high conductance, and prominent subconductance states. In addition to activation by Na(+), we report that rSLO-2 channels are cooperatively activated by intracellular Cl(-), similar to C. elegans SLO-2 channels. Since intracellular Na(+) and Cl(-) both rise in oxygen-deprived cells, coactivation may more effectively trigger the activity of rSLO-2 channels in ischemia. In C. elegans, mutational and physiological analysis revealed that the SLO-2 current is a major component of the delayed rectifier. We demonstrate in C. elegans that slo-2 mutants are hypersensitive to hypoxia, suggesting a conserved role for the slo-2 gene subfamily.
Yuan
Alex
A
Department of Anatomy and Neurobiology, Washington University School of Medicine, 660 S. Euclid Avenue, Saint Louis, MO 63110, USA.
Santi
Celia M
CM
Wei
Aguan
A
Wang
Zhao Wen
ZW
Pollak
Kelly
K
Nonet
Michael
M
Kaczmarek
Leonard
L
Crowder
C Michael
CM
Salkoff
Lawrence
L
D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans; D002478:Cells, Cultured; D005260:Female; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics; D008969:Molecular Sequence Data; D005810:Multigene Family; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D009865:Oocytes; D015221:Potassium Channels / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D024681:Potassium Channels, Calcium-Activated / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000081033:Potassium Channels, Sodium-Activated; D017386:Sequence Homology, Amino Acid; D012964:Sodium / Q000494:pharmacology; D014981:Xenopus
D051036:Large-Conductance Calcium-Activated Potassium Channels; D009419:Nerve Tissue Proteins; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D000081033:Potassium Channels, Sodium-Activated; C000626167:kcnt1 protein, rat; D012964:Sodium