ERK integrates PKA and PKC signaling in superficial dorsal horn neurons. I. Modulation of A-type K+ currents.

The transient outward potassium currents (also known as A-type currents or IA) are important determinants of neuronal excitability. In the brain, IA is modulated by protein kinase C (PKC), protein kinase A (PKA), and extracellular signal-related kinase (ERK), three kinases that have been shown to be critical modulators of nociception. We wanted to determine the effects of these kinases on IA in superficial dorsal horn neurons. Using whole cell recordings from cultured mouse spinal cord superficial dorsal horn neurons, we found that PKC and PKA both inhibit IA in these cells, and that PKC has a tonic inhibitory action on IA. Further, we provide evidence supporting the hypothesis that PKC and PKA do not modulate IA directly, but rather act as upstream activators of ERKs, which modulate IA. These results suggest that ERKs serve as signal integrators in modulation of IA in dorsal horn neurons and that modulation of A-type potassium currents may underlie aspects of central sensitization mediated by PKC, PKA, and ERKs.