TY - JOUR
T1 - The sodium-activated potassium channel is encoded by a member of the Slo gene family
AU - Yuan, Alex
AU - Santi, Celia M.
AU - Wei, Aguan
AU - Wang, Zhao Wen
AU - Pollak, Kelly
AU - Nonet, Michael
AU - Kaczmarek, Leonard
AU - Crowder, C. Michael
AU - Salkoff, Lawrence
N1 - Funding Information:
Supported by grants from the NIH to L.S. and the Washington University McDonnell Center for Cellular and Molecular Neurobiology. We also thank Bill Joiner, Alice Butler, and Gloria Fawcett for help and advice.
PY - 2003/3/6
Y1 - 2003/3/6
N2 - Na+-activated potassium channels (KNa) have been identified in cardiomyocytes and neurons where they may provide protection against ischemia. We now report that KNa 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 KNa 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.
AB - Na+-activated potassium channels (KNa) have been identified in cardiomyocytes and neurons where they may provide protection against ischemia. We now report that KNa 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 KNa 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.
UR - http://www.scopus.com/inward/record.url?scp=0037421995&partnerID=8YFLogxK
U2 - 10.1016/S0896-6273(03)00096-5
DO - 10.1016/S0896-6273(03)00096-5
M3 - Article
C2 - 12628167
AN - SCOPUS:0037421995
SN - 0896-6273
VL - 37
SP - 765
EP - 773
JO - Neuron
JF - Neuron
IS - 5
ER -