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PMID: 20670831 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Modulation of high-voltage activated Ca(2+) channels by membrane phosphatidylinositol 4,5-bisphosphate.

Neuron ·Vol. 67 ·No. 2 ·2010-07-29 ·Pages 224-38

Suh BC, Leal K, Hille B

Abstract

Modulation of voltage-gated Ca(2+) channels controls activities of excitable cells. We show that high-voltage activated Ca(2+) channels are regulated by membrane phosphatidylinositol 4,5-bisphosphate (PIP(2)) with different sensitivities. Plasma membrane PIP(2) depletion by rapamycin-induced translocation of an inositol lipid 5-phosphatase or by a voltage-sensitive 5-phosphatase (VSP) suppresses Ca(V)1.2 and Ca(V)1.3 channel currents by approximately 35% and Ca(V)2.1 and Ca(V)2.2 currents by 29% and 55%, respectively. Other Ca(V) channels are less sensitive. Inhibition is not relieved by strong depolarizing prepulses. It changes the voltage dependence of channel gating little. Recovery of currents from inhibition needs intracellular hydrolysable ATP, presumably for PIP(2) resynthesis. When PIP(2) is increased by overexpressing PIP 5-kinase, activation and inactivation of Ca(V)2.2 current slow and voltage-dependent gating shifts to slightly higher voltages. Thus, endogenous membrane PIP(2) supports high-voltage activated L-, N-, and P/Q-type Ca(2+) channels, and stimuli that activate phospholipase C deplete PIP(2) and reduce those Ca(2+) channel currents.

MeSH Terms
Adenosine Triphosphate/analogs & derivatives,metabolism,pharmacology Barium/pharmacology Biophysics Calcium/metabolism Calcium Channels, L-Type/genetics,physiology Cell Line, Transformed Chelating Agents/pharmacology Egtazic Acid/analogs & derivatives,pharmacology Electric Stimulation/methods Fluorescence Resonance Energy Transfer/methods Green Fluorescent Proteins/genetics Humans Immunosuppressive Agents/pharmacology Ion Channel Gating/drug effects,genetics,physiology Membrane Potentials/drug effects,genetics Muscarinic Agonists/pharmacology Oxotremorine/pharmacology Patch-Clamp Techniques/methods Phosphatidylinositol 4,5-Diphosphate/metabolism Phosphoric Monoester Hydrolases/genetics,pharmacology Sirolimus/pharmacology Time Factors Transfection
Chemicals
CACNA1D protein, human Calcium Channels, L-Type Chelating Agents Immunosuppressive Agents L-type calcium channel alpha(1C) Muscarinic Agonists Phosphatidylinositol 4,5-Diphosphate Green Fluorescent Proteins Barium 5'-adenylyl (beta,gamma-methylene)diphosphonate Egtazic Acid Oxotremorine Adenosine Triphosphate voltage-sensor-containing phosphatase, Ciona intestinalis Phosphoric Monoester Hydrolases 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid Calcium Sirolimus
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Suh Byung-Chang
Department of Physiology and Biophysics, The University of Washington School of Medicine, Seattle, WA 98195-7290, USA. [email protected]
Leal Karina
Hille Bertil
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Article Info
Journal
Neuron
Abbr.
Neuron
ISSN
1097-4199
DOI
10.1016/j.neuron.2010.07.001
Email
[email protected]
Published
2010-07-29
Pages
224-38
Language
English
Region
United States
NLM ID
8809320
PMCID
PMC2931829
Subset
IM
Grants
NIGMS NIH HHS · T32 GM007108 · United States
NINDS NIH HHS · R01 NS008174 · United States
NINDS NIH HHS · NS08174 · United States
NINDS NIH HHS · R37 NS008174 · United States
NINDS NIH HHS · R01 NS008174-43 · United States
NINDS NIH HHS · NS0222625 · United States
NIGMS NIH HHS · T32 GM07108 · United States
External Links
PubMed source DOI: 10.1016/j.neuron.2010.07.001 PMC Full Text View journal details
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