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.