期刊
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
卷 461, 期 1, 页码 177-189出版社
SPRINGER
DOI: 10.1007/s00424-010-0898-x
关键词
BKCa channel; Cytosolic free Ca2+ elevation; Endothelial cells; Hyperpolarization; Membrane potential; Lipid mediators; Lysophosphatidylinositol
类别
资金
- Austrian Science Funds, FWF [P20181-B05, 21857-B18, F3010-B05]
- Austrian Ministry of Education, Science and Culture
- Austrian Science Fund (FWF) [P 21857] Funding Source: researchfish
Lysophospholipids are known to serve as intra- and extracellular messengers affecting many physiological processes. Lysophosphatidylinositol (LPI), which is produced in endothelial cells, acts as an endogenous agonist of the orphan receptor, G protein-coupled receptor 55 (GPR55). Stimulation of GPR55 by LPI evokes an intracellular Ca2+ rise in several cell types including endothelial cells. In this study, we investigated additional direct, receptor-independent effects of LPI on endothelial large-conductance Ca2+ and voltage-gated potassium (BKCa) channels. Electrophysiological experiments in the inside-out configuration revealed that LPI directly affects the BKCa channel gating properties. This effect of LPI strictly depended on the presence of Ca2+ and was concentration-dependent, reversible, and dual in nature. The modulating effects of LPI on endothelial BKCa channels correlated with their initial open probability (Po): stimulation at low Po (<0.3) and inhibition at high Po levels (>0.3). In the whole-cell configuration, LPI in the pipette facilitated membrane hyperpolarization in response to low (0.1-2 mu M) histamine concentrations. In contrast, LPI counteracted membrane hyperpolarization in response to supramaximal cell stimulation with histamine. These results highlight a novel receptor-independent and direct bidirectional modulation of BKCa channels by LPI on endothelial cells. We conclude that LPI via this mechanism serves as an important modulator of endothelial electrical responses to cell stimulation.
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