title: Voltage-activated proton currents in human THP-1 monocytes.
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, gH, activated slowly during depolarizing pulses, with a sigmoidal time course. Fitted by a single exponential following a delay, the activation time constant, tauact 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, tautail, was voltage dependent, decreasing with hyperpolarization from 2-3 sec at 0 mV to approximately 200 msec at -100 mV. Surprisingly, although tauact depended strongly on pHo, tautail was completely independent of pHo. H+ currents were inhibited by Zn2+. Increasing pHo or decreasing pHi shifted the voltage-activation relationship to more negative potentials, tending to activate the gH 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., pHi). In THP-1 cells differentiated into macrophages, the H+ current density was reduced by one-half, and tauact was slower by about twofold. The properties of H+ channels in THP-1 cells and in other macrophage-related cells are compared.
authors.affiliation: Department of Molecular Biophysics and Physiology, Rush Presbyterian St. Luke's Medical Center, 1653 West Congress Parkway, Chicago, IL 60612, USA.
authors.forename: T E
authors.initials: TE
authors.lastname: DeCoursey
authors.forename: V V
authors.initials: VV
authors.lastname: Cherny
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D004558:Electric Stimulation; D006801:Humans; D006863:Hydrogen-Ion Concentration; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D007948:Leukemia, Monocytic, Acute / Q000378:metabolism / Q000473:pathology*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008322:Mammals / Q000502:physiology; D009000:Monocytes / Q000187:drug effects / Q000502:physiology*; D009363:Neoplasm Proteins / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011522:Protons; D012908:Snails / Q000502:physiology; D013045:Species Specificity; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D007473:Ion Channels; D009363:Neoplasm Proteins; D011522:Protons; D013755:Tetradecanoylphorbol Acetate