Blockade of GABA and glycine reuptake differentially affects temporal and spectral characteristics of phrenic nerve discharge in arterially‐perfused adult rat

Abstract

Fast synaptic inhibition plays an essential role in control of the central respiratory network. Recently, we have shown that blockade of GABAA and glycine receptors in an arterially‐perfused adult rat preparation alters the temporal and spectral characteristics of phrenic nerve discharge and markedly reduces inspiratory network complexity. The influence of excess endogenous GABA and glycine on phrenic motor output, however, is not known. Therefore, we examined the effects of blockade of GABA and glycine reuptake using sarcosine (SAR; n=6) and nipecotic acid (NA; n=5), respectively, on phrenic nerve discharge in the same preparation. Perfusion with either reuptake blocker (100 mM) ultimately abolished phrenic nerve discharge; the effects of SAR resulted from a decrease in burst amplitude (P=0.0001) while those of NA resulted from a decrease in burst frequency (P=0.004). SAR and NA slightly enhanced MFO spectral power; however, HFO spectral power was differentially affected (i.e., SAR decreased; NA increased). Inspiratory network complexity (approximate entropy) was unchanged by SAR or NA. These data demonstrate that excess endogenous GABA and glycine differentially modulate the temporal and spectral characteristics of phrenic nerve discharge, providing additional evidence supporting separate and distinct roles for GABA and glycine in central respiratory neural control. Support: NS045321, NS049310