title: The GPR55 agonist lysophosphatidylinositol directly activates intermediate-conductance Ca2+ -activated K+ channels.
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.
authors: Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University of Graz, Harrachgasse 21/III, Graz, Austria.
authors: Alexander I
authors: AI
authors: Bondarenko
authors: Roland
authors: R
authors: Malli
authors: Wolfgang F
authors: WF
authors: Graier
references: J Biol Chem. 2000 Apr 7;275(14):10128-33
references: 10744694
references: Am J Physiol Heart Circ Physiol. 2001 Jun;280(6):H2478-83
references: 11356601
references: Br J Pharmacol. 2009 Feb;156(4):545-62
references: 19187341
references: Neuroscience. 2002;109(4):827-35
references: 11927165
references: Biochem Biophys Res Commun. 2007 Nov 3;362(4):928-34
references: 17765871
references: Br J Pharmacol. 1999 Nov;128(5):1064-70
references: 10556944
references: Naunyn Schmiedebergs Arch Pharmacol. 2008 Apr;377(2):101-9
references: 18264694
references: Clin Exp Pharmacol Physiol. 2002 Jul;29(7):630-7
references: 12060109
references: J Physiol. 1996 Apr 1;492 ( Pt 1):53-60
references: 8730582
references: Biochim Biophys Acta. 2002 May 23;1582(1-3):52-69
references: 12069810
references: Br J Pharmacol. 1988 Sep;95(1):189-96
references: 3064851
references: Biochim Biophys Acta. 2008 Sep;1781(9):531-9
references: 18407842
references: FASEB J. 2009 Apr;23(4):1138-45
references: 19074509
references: Biochim Biophys Acta. 2002 May 23;1582(1-3):216-21
references: 12069831
references: FASEB J. 2009 Jan;23(1):183-93
references: 18757503
references: Br J Pharmacol. 2010 Sep;161(2):308-20
references: 20735417
references: J Neurosci. 2007 Mar 21;27(12):3347-55
references: 17376995
references: Pflugers Arch. 2011 Jan;461(1):177-89
references: 21072666
references: J Biol Chem. 2006 Dec 29;281(52):40174-82
references: 17082190
references: Br J Pharmacol. 2005 Feb;144(4):477-85
references: 15655533
references: J Biol Chem. 2006 Feb 24;281(8):4977-82
references: 16368680
references: J Cell Sci. 2008 May 15;121(Pt 10):1704-1717
references: 18445684
references: Circ Res. 2000 Sep 15;87(6):496-503
references: 10988242
references: J Gen Physiol. 1994 Oct;104(4):645-73
references: 7530766
references: Am J Physiol Cell Physiol. 2006 Apr;290(4):C1000-8
references: 16267108
references: Proc Natl Acad Sci U S A. 1983 Jun;80(12):3734-7
references: 6407019
references: Am J Physiol Cell Physiol. 2000 Mar;278(3):C570-81
references: 10712246
references: Eur J Biochem. 1994 Apr 1;221(1):383-9
references: 8168525
references: Anal Biochem. 2001 Mar;290(2):302-13
references: 11237333
references: Anal Biochem. 1984 Jun;139(2):408-12
references: 6476378
references: Pflugers Arch. 2009 Nov;459(1):71-7
references: 19680683
references: Am J Physiol Cell Physiol. 2007 Jul;293(1):C458-67
references: 17459950
references: J Membr Biol. 1998 Sep 15;165(2):133-43
references: 9745001
references: J Cardiovasc Pharmacol. 1994 May;23(5):747-56
references: 7521457