ERK Integrates PKA and PKC Signaling in Superficial Dorsal Horn Neurons. I. Modulation of A-Type K super(+) Currents

The transient outward potassium currents (also known as A-type currents or I sub(A)) are important determinants of neuronal excitability. In the brain, I sub(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 sub(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 sub(A) in these cells, and that PKC has a tonic inhibitory action on I sub(A). Further, we provide evidence supporting the hypothesis that PKC and PKA do not modulate I sub(A) directly, but rather act as upstream activators of ERKs, which modulate I sub(A). These results suggest that ERKs serve as signal integrators in modulation of I sub(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.