Activity of KCNQ (Kv7) channels requires binding of phosphatidylinositol 4,5-bisphosphate (PIP2) from the plasma membrane. We give evidence that Mg2+ and polyamines weaken the KCNQ channel–phospholipid interaction. Lowering internal Mg2+ augmented inward and outward KCNQ currents symmetrically, and raising Mg2+ reduced currents symmetrically. Polyvalent organic cations added to the pipette solution had similar effects. Their potency sequence followed the number of positive charges: putrescine (+2) < spermidine (+3) < spermine (+4) < neomycin (+6) < polylysine (≫+6). The inhibitory effects of Mg2+ were reversible with sequential whole-cell patching. Internal tetraethylammonium ion (TEA) gave classical voltage-dependent block of the pore with changes of the time course of K+ currents. The effect of polyvalent cations was simpler, symmetric, and without changes of current time course. Overexpression of phosphatidylinositol 4-phosphate 5-kinase Iγ to accelerate synthesis of PIP2 attenuated the sensitivity to polyvalent cations. We suggest that Mg2+ and other polycations reduce the currents by electrostatic binding to the negative charges of PIP2, competitively reducing the amount of free PIP2 available for interaction with channels. The dose–response curves could be modeled by a competition model that reduces the pool of free PIP2. This mechanism is likely to modulate many other PIP2-dependent ion channels and cellular processes.
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1 September 2007
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August 27 2007
Electrostatic Interaction of Internal Mg2+ with Membrane PIP2 Seen with KCNQ K+ Channels
Byung-Chang Suh,
Byung-Chang Suh
Department of Physiology and Biophysics, University of Washington School of Medicine, Seattle, WA 98195
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Bertil Hille
Bertil Hille
Department of Physiology and Biophysics, University of Washington School of Medicine, Seattle, WA 98195
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Byung-Chang Suh
Department of Physiology and Biophysics, University of Washington School of Medicine, Seattle, WA 98195
Bertil Hille
Department of Physiology and Biophysics, University of Washington School of Medicine, Seattle, WA 98195
Correspondence to Bertil Hille: [email protected]
Abbreviations used in this paper: IP3, inositol 1,4,5-trisphosphate; PIP, phosphatidylinositol 4-phosphate; PIP2, phosphatidylinositol 4,5-bisphosphate; Oxo-M, oxotremorine-M; TEA, tetraethylammonium ion; PIPKIγ, phosphatidylinositol 4-phosphate 5-kinase Iγ.
Received:
May 15 2007
Accepted:
August 01 2007
Online ISSN: 1540-7748
Print ISSN: 0022-1295
The Rockefeller University Press
2007
J Gen Physiol (2007) 130 (3): 241–256.
Article history
Received:
May 15 2007
Accepted:
August 01 2007
Citation
Byung-Chang Suh, Bertil Hille; Electrostatic Interaction of Internal Mg2+ with Membrane PIP2 Seen with KCNQ K+ Channels . J Gen Physiol 1 September 2007; 130 (3): 241–256. doi: https://doi.org/10.1085/jgp.200709821
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