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PIP2 hydrolysis underlies agonist-induced inhibition and regulates voltage gating of two-pore domain K+ channels.
Lopes CM, Rohács T, Czirják G, Balla T, Enyedi P, Logothetis DE.
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Two-pore (2-P) domain potassium channels are implicated in the control of the resting membrane potential, hormonal secretion, and the amplitude, frequency and duration of the action potential. These channels are strongly regulated by hormones and neurotransmitters. Little is known, however, about the mechanism underlying their regulation. Here we show that phosphatidylinositol 4,5-bisphosphate (PIP2) gating underlies several aspects of 2-P channel regulation. Our results demonstrate that all four 2-P channels tested, TASK1, TASK3, TREK1 and TRAAK are activated by PIP2. We show that mechanical stimulation may promote PIP2 activation of TRAAK channels. For TREK1, TASK1 and TASK3 channels, PIP2 hydrolysis underlies inhibition by several agonists. The kinetics of inhibition by the PIP2 scavenger polylysine, and the inhibition by the phosphatidylinositol 4-kinase inhibitor wortmannin correlated with the level of agonist-induced inhibition. This finding suggests that the strength of channel PIP2 interactions determines the extent of PLC-induced inhibition. Finally, we show that PIP2 hydrolysis modulates voltage dependence of TREK1 channels and the unrelated voltage-dependent KCNQ1 channels. Our results suggest that PIP2 is a common gating molecule for K+ channel families despite their distinct structures and physiological properties.
Baukrowitz,
PIP2 and PIP as determinants for ATP inhibition of KATP channels.
1998, Pubmed,
Xenbase
Baukrowitz,
PIP2 and PIP as determinants for ATP inhibition of KATP channels.
1998,
Pubmed
,
Xenbase Bockenhauer,
KCNK2: reversible conversion of a hippocampal potassium leak into a voltage-dependent channel.
2001,
Pubmed
,
Xenbase Brickley,
Adaptive regulation of neuronal excitability by a voltage-independent potassium conductance.
2001,
Pubmed Chemin,
Mechanisms underlying excitatory effects of group I metabotropic glutamate receptors via inhibition of 2P domain K+ channels.
2003,
Pubmed Chuang,
Bradykinin and nerve growth factor release the capsaicin receptor from PtdIns(4,5)P2-mediated inhibition.
2001,
Pubmed
,
Xenbase Czirják,
TASK-3 dominates the background potassium conductance in rat adrenal glomerulosa cells.
2002,
Pubmed
,
Xenbase Czirják,
Inhibition of TASK-1 potassium channel by phospholipase C.
2001,
Pubmed
,
Xenbase Czirják,
TASK (TWIK-related acid-sensitive K+ channel) is expressed in glomerulosa cells of rat adrenal cortex and inhibited by angiotensin II.
2000,
Pubmed
,
Xenbase Duprat,
TASK, a human background K+ channel to sense external pH variations near physiological pH.
1997,
Pubmed
,
Xenbase Fink,
Cloning, functional expression and brain localization of a novel unconventional outward rectifier K+ channel.
1996,
Pubmed
,
Xenbase Goldstein,
Potassium leak channels and the KCNK family of two-P-domain subunits.
2001,
Pubmed Hilgemann,
Regulation of cardiac Na+,Ca2+ exchange and KATP potassium channels by PIP2.
1996,
Pubmed Hilgemann,
The complex and intriguing lives of PIP2 with ion channels and transporters.
2001,
Pubmed Huang,
Direct activation of inward rectifier potassium channels by PIP2 and its stabilization by Gbetagamma.
1998,
Pubmed
,
Xenbase Kim,
Synergistic interaction and the role of C-terminus in the activation of TRAAK K+ channels by pressure, free fatty acids and alkali.
2001,
Pubmed Kobrinsky,
Receptor-mediated hydrolysis of plasma membrane messenger PIP2 leads to K+-current desensitization.
2000,
Pubmed
,
Xenbase Lesage,
Molecular and functional properties of two-pore-domain potassium channels.
2000,
Pubmed Liman,
Subunit stoichiometry of a mammalian K+ channel determined by construction of multimeric cDNAs.
1992,
Pubmed
,
Xenbase Lopes,
Proton block and voltage gating are potassium-dependent in the cardiac leak channel Kcnk3.
2000,
Pubmed
,
Xenbase Lopes,
Alterations in conserved Kir channel-PIP2 interactions underlie channelopathies.
2002,
Pubmed
,
Xenbase Loussouarn,
Phosphatidylinositol-4,5-bisphosphate, PIP2, controls KCNQ1/KCNE1 voltage-gated potassium channels: a functional homology between voltage-gated and inward rectifier K+ channels.
2003,
Pubmed Maingret,
Molecular basis of the voltage-dependent gating of TREK-1, a mechano-sensitive K(+) channel.
2002,
Pubmed Millar,
A functional role for the two-pore domain potassium channel TASK-1 in cerebellar granule neurons.
2000,
Pubmed
,
Xenbase Nakanishi,
A wortmannin-sensitive phosphatidylinositol 4-kinase that regulates hormone-sensitive pools of inositolphospholipids.
1995,
Pubmed Patel,
Inhalational anesthetics activate two-pore-domain background K+ channels.
1999,
Pubmed Patel,
Properties and modulation of mammalian 2P domain K+ channels.
2001,
Pubmed Rohács,
Assaying phosphatidylinositol bisphosphate regulation of potassium channels.
2002,
Pubmed
,
Xenbase Rohács,
Specificity of activation by phosphoinositides determines lipid regulation of Kir channels.
2003,
Pubmed
,
Xenbase Runnels,
The TRPM7 channel is inactivated by PIP(2) hydrolysis.
2002,
Pubmed Shyng,
Membrane phospholipid control of nucleotide sensitivity of KATP channels.
1998,
Pubmed Sirois,
The TASK-1 two-pore domain K+ channel is a molecular substrate for neuronal effects of inhalation anesthetics.
2000,
Pubmed Stauffer,
Receptor-induced transient reduction in plasma membrane PtdIns(4,5)P2 concentration monitored in living cells.
1998,
Pubmed Suh,
Recovery from muscarinic modulation of M current channels requires phosphatidylinositol 4,5-bisphosphate synthesis.
2002,
Pubmed Sui,
Activation of the atrial KACh channel by the betagamma subunits of G proteins or intracellular Na+ ions depends on the presence of phosphatidylinositol phosphates.
1998,
Pubmed
,
Xenbase Talley,
Modulation of TASK-1 (Kcnk3) and TASK-3 (Kcnk9) potassium channels: volatile anesthetics and neurotransmitters share a molecular site of action.
2002,
Pubmed Talley,
TASK-1, a two-pore domain K+ channel, is modulated by multiple neurotransmitters in motoneurons.
2000,
Pubmed van der Wal,
Monitoring agonist-induced phospholipase C activation in live cells by fluorescence resonance energy transfer.
2001,
Pubmed Várnai,
Visualization of phosphoinositides that bind pleckstrin homology domains: calcium- and agonist-induced dynamic changes and relationship to myo-[3H]inositol-labeled phosphoinositide pools.
1998,
Pubmed Wu,
Dual regulation of voltage-gated calcium channels by PtdIns(4,5)P2.
2002,
Pubmed
,
Xenbase Xie,
Phospholipase C-linked receptors regulate the ATP-sensitive potassium channel by means of phosphatidylinositol 4,5-bisphosphate metabolism.
1999,
Pubmed Zhang,
Activation of inwardly rectifying K+ channels by distinct PtdIns(4,5)P2 interactions.
1999,
Pubmed
,
Xenbase Zhang,
PIP(2) activates KCNQ channels, and its hydrolysis underlies receptor-mediated inhibition of M currents.
2003,
Pubmed
,
Xenbase
