The membrane electrical properties of undifferentiated pheochromocytoma cells of the rat (PC12) were studied using both current-and voltage-clamp techniques with the use of low-resistance blunt-tipped micropipettes (patch electrodes). In the presence of tetrodotoxin (TTX, 2-3 ~tM), a spike-like wave form with a prominent afterhyperpolarization (AHP) was recorded following brief (< 10ms) depolarizing current pulses. The inorganic divalent cations, Cd 2+ (0.5 mM), Mn 2 Β§ (4 mM), and 0 mM Ca 2 +/4 mM Mg 2+ solution prolonged the duration, attenuated the AHP, slowed the rate of repolarization, and slightly enhanced the amplitude of this wave form. A rapidly inactivating outward current was recorded in over 70% of the cells under voltage-clamp conditions. This transient current was elicited at about -30mV, and was blocked by tetraethylammonium (5 mM), inorganic divalent cations (Cd 2+, 0.5 mM; Mn 2+, 4 raM; Ba 2+, 3 raM), and removal of Ca 2 Β§ (0 mM Ca 2 +/4 mM Mg 2 Β§ from the local perfusion medium. In addition, 4-aminopyridine (5 raM), which blocks the transient outward K Β§ current IA in a variety of excitable cells, did not have any appreciable effect on this rapidly inactivating current. Moreover, it was possible to elicit the current at a holding potential of -40 mV. The reversal potential of this current was -90 mV, and shifted positively when extracellular K Β§ concentrations were elevated. It is concluded that PC12 cells have a rapidly inactivating Ca2+-dependent K Β§ current. A possible explanation for the transient nature of this current may be the presence of an effective intracellular Ca 2 Β§ buffering (uptake or extrusion) system.