Voltage-activated proton currents in human THP-1 monocytes.

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.