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SHR Neuro Krebs Kardio Lipid

Bondarenko, AI; Malli, R; Graier, WF.
The GPR55 agonist lysophosphatidylinositol directly activates intermediate-conductance Ca2+ -activated K+ channels.
Pflugers Arch. 2011; 462(2):245-255 [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG

 

Autor/innen der Med Uni Graz:
Bondarenko Oleksandr
Graier Wolfgang
Malli Roland
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Number of Figures: 7
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Abstract:
Lysophosphatidylinositol (LPI) was recently shown to act both as an extracellular mediator binding to G protein-coupled receptor 55 (GPR55) and as an intracellular messenger directly affecting a number of ion channels including large-conductance Ca(2+) and voltage-gated potassium (BK(Ca)) channels. Here, we explored the effect of LPI on intermediate-conductance Ca(2+)-activated K(+) (IK(Ca)) channels using excised inside-out patches from endothelial cells. The functional expression of IK(Ca) was confirmed by the charybdotoxin- and TRAM-34-sensitive hyperpolarization to histamine and ATP. Moreover, the presence of single IK(Ca) channels with a slope conductance of 39 pS in symmetric K(+) gradient was directly confirmed in inside-out patches. When cytosolically applied in the range of concentrations of 0.3-10 μM, which are well below the herein determined critical micelle concentration of approximately 30 μM, LPI potentiated the IK(Ca) single-channel activity in a concentration-dependent manner, while single-channel current amplitude was not affected. In the whole-cell configuration, LPI in the pipette was found to facilitate membrane hyperpolarization in response to low (0.5 μM) histamine concentrations in a TRAM-34-sensitive manner. These results demonstrate a so far not-described receptor-independent effect of LPI on the IK(Ca) single-channel activity of endothelial cells, thus, highlighting LPI as a potent intracellular messenger capable of modulating electrical responses in the vasculature.
Find related publications in this database (using NLM MeSH Indexing)
Cell Line -
Charybdotoxin - pharmacology
Endothelial Cells - drug effects
Histamine - pharmacology
Histamine Agonists - pharmacology
Humans -
Lysophospholipids - metabolism
Neurotoxins - pharmacology
Patch-Clamp Techniques -
Peptides - pharmacology
Potassium Channels, Calcium-Activated - metabolism
Pyrazoles - pharmacology
Receptors, G-Protein-Coupled - agonists

Find related publications in this database (Keywords)
IK(Ca) channel
Cytosolic free Ca(2+) elevation
Endothelial cells
Hyperpolarization
Membrane potential
Lipid mediators
Lysophosphatidylinositol
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