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 I-A) are important determinants of neuronal excitability. In the brain, I-A 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 I-A 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 I-A in these cells, and that PKC has a tonic inhibitory action on I-A. Further, we provide evidence supporting the hypothesis that PKC and PKA do not modulate I-A directly, but rather act as upstream activators of ERKs, which modulate I-A. These results suggest that ERKs serve as signal integrators in modulation of I-A in dorsal horn neurons and that modulation of A-type potassium currents may underlie aspects of central sensitization mediated by PKC, PKA, and ERKs.