VCAM-1-induced inwardly rectifying K(+) current enhances Ca(2+) entry in human THP-1 monocytes.
Hyperpolarization in human leukemia THP-1 monocytes adherent to vascular cell adhesion molecule (VCAM)-1 is due to an induction of inwardly rectifying K(+) currents (I(ir)) (Colden-Stanfield M and Gallin EK, Am J Physiol Cell Physiol 275: C267-C277, 1998). We determined whether the VCAM-1-induced hyperpolarization is sufficient to augment the increase in intracellular free calcium ([Ca(2+)](i)) produced by Ca(2+) store depletion with thapsigargin (TG) and readdition of external CaCl(2) in fura 2-loaded THP-1 monocytes. Whereas there was a 2.1-fold increase in [Ca(2+)](i) in monocytes bound to glass for 5 h in response to TG and CaCl(2) addition, adherence to VCAM-1 produced a 5-fold increase in [Ca(2+)](i). Depolarization of monocytes adherent to VCAM-1 by I(ir) blockade or exposure to high [K(+)] abolished the enhancement of the peak [Ca(2+)](i) response. In monocytes bound to glass, hyperpolarization of the membrane potential with valinomycin, a K(+) ionophore, to the level of hyperpolarization seen in cells adherent to VCAM-1 produced similar changes in peak [Ca(2+)](i). Adherence of monocytes to E-selectin produced a similar peak [Ca(2+)](i) to cells bound to glass. Thus monocyte adherence to the physiological substrate VCAM-1 produces a hyperpolarization that is sufficient to enhance Ca(2+) entry and may impact Ca(2+)-dependent monocyte function.
Department of Physiology, Morehouse School of Medicine, Atlanta, Georgia 30310, USA. stanfiel@msm.edu
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Colden-Stanfield
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Scanlon
D002118:Calcium / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D039041:Integrin alpha4beta1; D016023:Integrins / Q000187:drug effects / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D016201:Receptors, Lymphocyte Homing / Q000187:drug effects / Q000378:metabolism*; D019284:Thapsigargin / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000187:drug effects / Q000378:metabolism*
D004791:Enzyme Inhibitors; D039041:Integrin alpha4beta1; D016023:Integrins; D015221:Potassium Channels; D016201:Receptors, Lymphocyte Homing; D019010:Vascular Cell Adhesion Molecule-1; D019284:Thapsigargin; D002118:Calcium