Spinal atypical PKC activity is necessary for inactivity‐induced phrenic motor facilitation in Charles River Sprague Dawley rats with NMDA receptor inhibition

Abstract

A central neural apnea elicits an atypical protein kinase C (aPKC) dependent increase in phrenic amplitude when respiratory neural activity is restored, a form of plasticity known as inactivity-induced phrenic motor facilitation (iPMF). Spinal NMDA receptor activation constrains iPMF in Charles River Sprague Dawley (CRSD) rats. We tested the hypothesis that aPKC is necessary for iPMF maintenance in CRSD with NMDA receptor inhibition. Anesthetized and ventilated CRSD received an intrathecal NMDA receptor antagonist, APV (200ng), over C4 spinal segments prior to a hypocapnia-induced neural apnea. When phrenic activity was restored, CRSD with NMDA receptor inhibition had increased phrenic amplitude (15 min post- hypocapnia: 57 +/− 19% baseline, p < 0.05), indicating iPMF. Subsequent delivery of an intrathecal aPKC inhibitor, ZIP (20ug), abolished iPMF, similar to CRSD without NMDA receptor inhibition (60 min post-hypocapnia: 11 +/− 22% and −4 +/− 5% baseline, respectively, p > 0.05). CRSD with NMDA receptor inhibition and no ZIP continued to show iPMF (60 min post-hypocapnia: 64 +/− 8% baseline, p < 0.05). These data suggest that spinal aPKC is necessary for iPMF maintenance in CRSD with NMDA receptor inhibition, similar to iPMF in other strains that lack NMDA receptor constraint. We hypothesize that genetic or epigenetic differences in spinal NMDA receptors underlie strain differences in iPMF expression.