An outwardly rectifying conductance was observed in primary cultured h
uman epididymal cells under the patch-clamp whole-cell configuration i
n KCl pipette and bath solutions. Removal of Cl- from intracellular an
d extracellular solutions did not affect this conductance, but substit
ution of K+ with N-methyl-D-glucamine in both solutions completely blo
cked the current. The current magnitude was also found to be affected
by intracellular but not extracellular K+ concentrations. The conducta
nce could be inhibited by the cation channel blockers, barium and tetr
aethylammonium chloride. Single-channel recordings from the same cell
population also revealed the presence of a conductance of about 150 pS
with voltage dependence and blocker sensitivity similar to those obse
rved for the whole-cell current. This cation conductance was not affec
ted by changes in solution osmolarity but could be activated by extrac
ellular ATP. ATP activation of the conductance could be mimicked by io
nomycin and inhibited by BAPTA-AM, an agent that suppresses intracellu
lar free Ca2+. This ATP-regulated cation conductance may be responsibl
e for secreting K+ across the epididymal epithelium, resulting in an o
bserved K+ concentration much higher in the lumen of the epididymis th
an in the blood.