The protein IsK is a dual activator of K+ and Cl- channels.
The protein IsK (M(r) 14,500) is present in epithelial cells, heart, uterus and lymphocytes and induces slowly activating K+ currents when expressed in Xenopus oocytes. The finding that mutations of its single transmembrane segment altered channel gating or selectivity has suggested that IsK is a channel-forming protein. But IsK does not exhibit the K+ channel hallmarks (a conserved K+ selective pore (H5) flanked by either six or two membrane-spanning regions). Here we report that IsK expression in Xenopus oocytes also induces a Cl- selective current very similar to the Cl- current produced by phospholemman expression and with biophysical, pharmacological and regulation characteristics very different from those of the IsK-induced K+ channel activity. IsK mutagenesis identifies amino- and carboxy-terminal domains as critical for the induction of Cl- and K+ channel activities, respectively. Our data lead to a model in which the IsK protein (now called IsK, Cl) acts as a potent activator of endogenous and otherwise silent K+ or Cl- channels.
Attali
B
B
Institut de Pharmacologie Moléculaire et Cellulaire, CNRS, Valbonne, France.
Guillemare
E
E
Lesage
F
F
Honoré
E
E
Romey
G
G
Lazdunski
M
M
Barhanin
J
J
D000595:Amino Acid Sequence; D000818:Animals; D018118:Chloride Channels / Q000378:metabolism*; D003001:Cloning, Molecular; D004285:Dogs; D006801:Humans; D008564:Membrane Potentials; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D009865:Oocytes; D010750:Phosphoproteins / Q000378:metabolism; D015221:Potassium Channels / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated; D014981:Xenopus
D018118:Chloride Channels; D008565:Membrane Proteins; D010750:Phosphoproteins; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; C059983:potassium channel protein I(sk); C069141:phospholemman