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

1 Division of Neuroscience, Baylor College of Medicine, Houston, Texas 77030 2 Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas 77030 Submitted 8 April 2003; accepted in final form 7 May 2003 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. Address for reprint requests: Robert W. Gereau IV, Division of Neuroscience, Baylor College of Medicine, Houston, TX 77030 (E-mail: rgereau{at}bcm.tmc.edu ).