PKC regulates capsaicin-induced currents of dorsal root ganglion neurons in rats

Capsaicin activates a non-specific cation conductance in a subset of dorsal root ganglion (DRG) neurons. The inward current and membrane potential of acutely isolated DRG neurons were examined using whole-cell patch recording methods. We report here that the current and voltage responses activated b y capsaicin were markedly increased by phorbol 12-myristate 13-acetate (PMA ), an activator of protein kinase C (PKC). The mean current, after applicat ion of 0.3 muM PMA, was 153.5+/-5.7% of control (n=32) in Ca2+-free externa l solution and 181.6+/-6.8% of control (n=15) in standard external solution . Under current-clamp conditions, 0.3 muM PMA facilitated capsaicin-induced depolarization and action potential generation. Bindolylmaleimide I (BIM), a specific inhibitor of PKC activity, abolished the effect of PMA. In addi tion, capsaicin-evoked current was attenuated to 68.3+/-5.0% of control (n= 13) by individual administration of 1 muM BIM in standard external solution , while 0.3 muM BIM did not have this effect. These data suggest that PKC c an directly regulate the capsaicin response in DRG neurons, which could inc rease nociceptive sensory transmission and contribute to hyperalgesia. (C) 2001 Elsevier Science Ltd. All rights reserved.