By using the whole-cell patch-clamp technique, an inwardly rectifying potassium current, which resembled the "classic" inward-rectifying potassium current (IKIR) of other cells in terms of electrophysiological and pharmacological properties, was identified in db-cAMP-differentiated NG108-15 cells. First, the current was dependent on voltage and time. It could be elicited by applying an initial depolarizing prepulse and a subsequent hyperpolarizing command pulse to the cell. The amplitude of the current depended on both the prepulse and the command pulse and increased with the hyperpolarization of the command pulse as well as the depolarization and the prolongation of the prepulse. The activation and inactivation of the current could be fitted well by single-exponential functions and increased with the hyperpolarization of the membrane. Second, the current was dependent on the extracellular potassium concentration ([K+]o). Elevation of [K+]o resulted in a marked increase in the current amplitude and a positive shift of the peak-current/voltage curve as well as the reversal potential. A tenfold increase of [K+]o introduced an approximately 43-mV shift of the reversal potential, indicating that the current was carried mainly by K+. The conductance (g/gMax) of the current was also dependent on the [K+]o and increased with increases in [K+]o in a manner approximately proportional to the square-root of [K+]o. Finally, the current was sensitive to Cs+ (1 mmol/l), Ba2+ (1 mmol/l) and quinidine (0.2 mmol/l); whereas, two typical potassium channel inhibitors, tetraethylammonium (TEA) and 4-aminopyridine (4-AP), were weak blockers and reduced the current at high concentration (>10 mmol/l). It was also observed that the current was depressed by Cd2+ (1 mmol/l) and Co2+ (1 mmol/l) and increased by perfusing the cell with Ca2+-free solution. Thus, except for the sensitivity to Cd2+, Co2+ and Ca2+, the current displayed most of the hallmarks described for the "classic" IKIR. In conclusion, there appears to be a voltage-dependent IKIR-type inward rectifier in db-cAMP-differentiated NG108-15 cells.