Phosphatidylinositol-4,5-bisphosphate, PIP2, controls KCNQ1/KCNE1 voltage-gated potassium channels: a functional homology between voltage-gated and inward rectifier K+ channels.
Phosphatidylinositol-4,5-bisphosphate (PIP(2)) is a major signaling molecule implicated in the regulation of various ion transporters and channels. Here we show that PIP(2) and intracellular MgATP control the activity of the KCNQ1/KCNE1 potassium channel complex. In excised patch-clamp recordings, the KCNQ1/KCNE1 current decreased spontaneously with time. This rundown was markedly slowed by cytosolic application of PIP(2) and fully prevented by application of PIP(2) plus MgATP. PIP(2)-dependent rundown was accompanied by acceleration in the current deactivation kinetics, whereas the MgATP-dependent rundown was not. Cytosolic application of PIP(2) slowed deactivation kinetics and also shifted the voltage dependency of the channel activation toward negative potentials. Complex changes in the current characteristics induced by membrane PIP(2) was fully restituted by a model originally elaborated for ATP-regulated two transmembrane-domain potassium channels. The model is consistent with stabilization by PIP(2) of KCNQ1/KCNE1 channels in the open state. Our data suggest a striking functional homology between a six transmembrane-domain voltage-gated channel and a two transmembrane-domain ATP-gated channel.
Loussouarn
G
G
Institut National de la Santé et de la Recherche Médicale, INSERM U533 Laboratoire de Physiopathologie et de Pharmacologie Cellulaires et Moléculaires, Hôpital Hôtel-Dieu, Nantes, France. gildas.loussouarn@nantes.inserm.fr
Park
K-H
KH
Bellocq
C
C
Baró
I
I
Charpentier
F
F
Escande
D
D
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002118:Calcium / Q000494:pharmacology; D002522:Chlorocebus aethiops; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; D051658:KCNQ2 Potassium Channel; D007700:Kinetics; D008274:Magnesium / Q000494:pharmacology; D008969:Molecular Sequence Data; D018408:Patch-Clamp Techniques; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated; D017433:Protein Structure, Secondary; D014162:Transfection
D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; D051658:KCNQ2 Potassium Channel; D019269:Phosphatidylinositol 4,5-Diphosphate; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D024642:Potassium Channels, Voltage-Gated; D000255:Adenosine Triphosphate; D008274:Magnesium; D002118:Calcium