State-dependent modulation of sympathetic firing by α1-adrenoceptors requires constitutive PKC activity in the neonatal rat spinal cord.

Abstract

The central adrenergic and noradrenergic neurotransmitter systems diffusively affect the operation of the spinal neural network and dynamically gauge central sympathetic outflow. Using in vitro splanchnic nerve-thoracic spinal cord preparations as an experimental model, this study examined the intraspinal α1-adrenoceptor-meidated modulation of sympathetic firing behaviors. Several sympathetic single-fiber activities were simultaneously recorded. Application of phenylephrine (Phe, an α1-adrenoceptor agonist) increased, decreased or did not affect spontaneous firing. A log-log plot of the change ratios of the average firing rates (AFR) versus their basal AFR displays a linear data distribution. Thus, the heterogeneity in α1-adrenoceptor-mediated responses is well described by a power law function. Phe-induced power-law firing modulation (plFM) was sensitive to prazosin (Prz, an α1-adrenoceptor antagonist). Heparin (Hep, a competitive IP3 receptor blocker) and chelerythrine (Che, a protein kinase C inhibitor) also caused plFM. Phe-induced plFM persisted in the presence of Hep; however, it was occluded by Che pretreatment. Pair-wise analysis of single-fiber activities revealed synchronous sympathetic discharges. Application of Phe, Hep or Che suppressed synchronous discharges in fiber pairs with apparent correlated firing (ACF) and induced or potentiated synchronous discharges in those without or with minimal ACF. Thus, the basal activities of the sympathetic preganglionic neurons participate in determining the responses mediated by the activation of α1-adrenoceptors. This deterministic factor, which is intrinsic to spinal neural networks, helps the supraspinal adrenergic and noradrenergic systems differentially control their widely distributed neural targets.