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Inhibition of Ca²⁺-dependent K⁺ channels in rat carotid body type I cells by protein kinase C

C. Peers and E. Carpenter

1. 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.

2. Pretreatment of cells for 10 min at 37 °C with 4-phorbol 12,13-didecanoate (4-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).

3. 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 4-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.

4. Ca²⁺ channel current density was not significantly different in type I cells pretreated with 200 nM 4-PDD as compared with cells treated with the same concentration of TPA.

5. 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.

6. 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.

7. 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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