Whole‐cell patch clamp recordings were used to investigate the effects of protein kinase C (PKC) activation on K⁺ and Ca²⁺ currents in type I cells isolated from the rat carotid body. Pretreatment of cells for 10 min at 37 °C with 4α‐phorbol 12,13‐didecanoate (4α‐PDD, 200 nm), a phorbol ester which does not activate PKC, did not affect K⁺ current density as compared with cells pretreated with vehicle alone. By contrast, identical pretreatment with 200 nm 12‐O‐teradecanoylphorbol‐13‐acetate (TPA, a PKC activator) dramatically reduced K⁺ current density in type I cells. This effect was prevented by co‐incubation of cells with the PKC inhibitor bisindolylmaleimide (BIM, 3 μm). The sensitivity of K⁺ currents to inhibition by 200 μm Cd²⁺ (indicative of the presence of Ca²⁺‐dependent K⁺ channels) was markedly reduced in TPA‐treated cells as compared with sham‐treated cells, cells treated with 4α‐PDD, and cells treated with both TPA and BIM. Cd²⁺‐resistant K⁺ current densities were of similar magnitude in all four groups of cells, as were the input resistances determined over the voltage range −100 mV to −50 mV. Ca²⁺ channel current density was not significantly different in type I cells pretreated with 200 nm 4α‐PDD as compared with cells treated with the same concentration of TPA. The degree of inhibition of K⁺ currents caused by hypoxia (P_o2 15–20 mmHg) was unaltered by pretreatment of cells with 3 μm BIM. The resting membrane potential of cells pretreated with TPA was depolarized as compared with controls, and the Ca²⁺‐dependent K⁺ channel inhibitor iberiotoxin (20 nm) failed to depolarize these cells further. Our results suggest that activation of PKC causes a marked, selective inhibition of Ca²⁺‐dependent K⁺ currents in type I carotid body cells, but that PKC activation is unlikely to account for inhibition of these channels by acute hypoxia.

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