Permeation properties and modulation of an ionic current gated by histamine were measured in single endothelial cells from human umbilical cord veins by use of the patch-clamp technique in the ruptured-whole-cell mode or using perforated patches. We combined these current measurements with a microfluorimetric method to measure concomitantly free intracellular calcium concentration ([Ca2+]i). Application of histamine induced an intracellular calcium transient and an ionic current that reversed near 0 mV. The amplitude of the current ranged from -0.2 to -2 nA at -100 mV. The tonic rise in [Ca2+]i and the ionic current are partly due to Ca2+ influx. This Ca2+ entry pathway is also permeable for Ba2+ and Mn2+. The amplitude of the histamine-activated current was also closely correlated with the amplitude of the concomitant Ca2+ transient, suggesting that the latter is at least partially due to Ca2+ influx through histamine-activated channels. The reversal potential of the histamine-induced current was 7.6 +/- 4.1 mV (n = 14) when the calcium concentration in the bath solution ([Ca2+]o) was 1.5 mmol/l. With 10 mmol/l [Ca2+]o it was -13.7 +/- 4.7 mV and shifted to + 13.0 +/- 1.5 mV in nominally Ca(2+)-free solution (n = 3 cells). The amplitude of the current in Ca(2+)-free solution was enhanced compared to that in 10 mmol/l [Ca2+]o. The shift of the reversal potential and the concomitant change of the current amplitude suggest that the channel is permeable for calcium but has a smaller permeability for calcium than for monovalent cations.(ABSTRACT TRUNCATED AT 250 WORDS)