Modulation of K+ currents in monocytes by VCAM-1 and E-selectin on activated human endothelium.
Resting membrane potential (RMP) and whole cell currents were recorded in human THP-1 monocytes adherent to polystyrene, unstimulated human umbilical vein endothelial cells (HUVECs), lipopolysaccharide (LPS)-treated HUVECs, immobilized E-selectin, or vascular cell adhesion molecule 1 (VCAM-1) using the patch-clamp technique. RMP after 5 h on polystyrene was -24.3 +/- 1.7 mV (n = 42) with delayed rectifier K+ (Idr) and Cl- currents (ICl) present in >75% of the cells. Inwardly rectifying K+ currents (Iir) were present in only 14% of THP-1 cells. Adherence to unstimulated HUVECs or E-selectin for 5 h had no effect on Iir or ICl but decreased Idr. Five hours after adherence to LPS-treated HUVECs, outward currents were unchanged, but Iir was present in 81% of THP-1 cells. A twofold increase in Iir and a hyperpolarization (-41.3 +/- 3.7 mV, n = 16) were abolished by pretreatment of THP-1 cells with cycloheximide, a protein synthesis inhibitor, or herbimycin A, a tyrosine kinase inhibitor, or by pretreatment of the LPS-treated HUVECs with anti-VCAM-1. Only a brief (15-min) interaction between THP-1 cells and LPS-treated HUVECs was required to induce Iir expression 5 h later. THP-1 cells adherent to VCAM-1 exhibited similar conductances to cells adherent to LPS-treated HUVECs. Thus engagement of specific integrins results in selective modulation of different K+ conductances.
Department of Physiology, Morehouse School of Medicine, Atlanta, Georgia 30310, USA.
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M
Colden-Stanfield
E K
EK
Gallin
D002448:Cell Adhesion; D002460:Cell Line; D002478:Cells, Cultured; D018118:Chloride Channels / Q000187:drug effects / Q000502:physiology; D051668:Delayed Rectifier Potassium Channels; D019040:E-Selectin / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009000:Monocytes / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011137:Polystyrenes; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013997:Time Factors; D014471:Umbilical Veins; D019010:Vascular Cell Adhesion Molecule-1 / Q000494:pharmacology*
D018118:Chloride Channels; D051668:Delayed Rectifier Potassium Channels; D019040:E-Selectin; D008070:Lipopolysaccharides; D011137:Polystyrenes; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D019010:Vascular Cell Adhesion Molecule-1