Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
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
Doi: 10.1007/s00424-011-0977-7
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- Führende Autor*innen der Med Uni Graz
- Bondarenko Oleksandr
- Graier Wolfgang
- Co-Autor*innen der Med Uni Graz
- Malli Roland
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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