Single K + channel currents were recorded in excised membrane patches from dispersed chemoreceptor cells of the rabbit carotid body under conditions that abolish current flow through Na + and Ca 2+ channels. We have found three classes of voltage-gated K + channels that differ in their single-channel conductance (~/), dependence on internal Ca 2+ (Cai2+), and sensitivity to changes in 02 tension (Po2). Ca2+-activated K + channels (Kca channels) with ~/ ~ 210 pS in symmetrical K + solutions were observed when [Ca2+]i was > 0.1 IzM. Small conductance channels with ~/= 16 pS were not affected by [Ca2+]i and they exhibited slow activation and inactivation time courses. In these two channel types open probability (Pop,n) was unaffected when exposed to normoxic (Po2 = 140 mmHg) or hypoxic (P02 -5-10 mmHg) external solutions. A third channel type (referred to as Ko 2 channel), having an intermediate ,/( ~ 40 pS), was the most frequently recorded. Ko~ channels are steeply voltage dependent and not affected by [Ca2+]i, they inactivate almost completely in < 500 ms, and their Pope, reversibly decreases upon exposure to low P02. The effect of low Po2 is voltage dependent, being more pronounced at moderately depolarized voltages. At 0 mV, for example, Popen diminishes to ~ 40% of the control value. The time course of ensemble current averages of Ko 2 channels is remarkably similar to that of the O2-sensitive K + current. In addition, ensemble average and macroscopic K + currents are affected similarly by low P02. These observations strongly suggest that Ko 2 channels are the main contributors to the macroscopic K + current of glomus cells. The reversible inhibition of Ko 2 channel activity by low P02 does not desensitize and is not related to the presence of F-, ATP, and GTP--¢-S at the internal face of the membrane. These results indicate that Ko 2 channels confer upon glomus cells their unique chemoreceptor properties and that the O2-K + channel interaction occurs either directly or through an O2 sensor intrinsic to the plasma membrane closely associated with the channel molecule.