II. Voltage-activated Proton Currents in Human THP-1 Monocytes |
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Authors: | TE DeCoursey VV Cherny |
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Institution: | (1) Department of Molecular Biophysics and Physiology, Rush Presbyterian St. Luke's Medical Center, 1653 West Congress Parkway, Chicago, IL 60612, US |
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Abstract: | Depolarization-activated H+-selective currents were studied using whole-cell and excised-patch voltage clamp methods in human monocytic leukemia THP-1
cells, before and after being induced by phorbol ester to differentiate into macrophage-like cells. The H+ conductance, g
H, activated slowly during depolarizing pulses, with a sigmoidal time course. Fitted by a single exponential following a delay,
the activation time constant, τact was roughly 10 sec at threshold potentials, decreasing at more positive potentials. Tail currents upon repolarization decayed
mono-exponentially at all potentials. The tail current time constant, τtail, was voltage dependent, decreasing with hyperpolarization from 2–3 sec at 0 mV to ∼200 msec at −100 mV. Surprisingly, although
τact depended strongly on pH
o
, τtail was completely independent of pH
o
. H+ currents were inhibited by Zn2+. Increasing pH
o
or decreasing pH
i
shifted the voltage-activation relationship to more negative potentials, tending to activate the g
H at any given voltage. Studied in excised, inside-out membrane patches, H+ currents were larger and activated much more rapidly at lower bath pH (i.e., pH
i
). In THP-1 cells differentiated into macrophages, the H+ current density was reduced by one-half, and τact was slower by about twofold. The properties of H+ channels in THP-1 cells and in other macrophage-related cells are compared.
Received: 19 September 1995/Revised: 14 March 1996 |
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Keywords: | : THP-1 — Proton channels — Macrophage — Phagocytes — Monocyte — pH |
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