Blockade of neuronal gap junctions modifies slow and fast oscillatory rhythms in phrenic nerve discharge in arterially‐perfused adult rat

Abstract

We have previously demonstrated that pharmacological blockade of gap junctions alters respiratory rhythm, phrenic burst pattern, and inspiratory‐phase synchronization. The pharmacological agents used to block functional gap junction coupling, however, were not specific to gap junctions composed of a specific connexin (Cx) isoform, and therefore may have exerted their effects on both neuronal and astrocytic gap junctions. To further delineate the role of neuronal gap junctions in central respiratory control, we examined the effects of mefloquine (MEQ; 0.5‐1.0 μM), which blocks neuron‐specific Cx36‐containing gap junctions, on phrenic nerve discharge in 5 arterially‐perfused adult rat preparations. We found that perfusion with MEQ increased phrenic burst frequency by 35±4% (P<0.001) due to decreases in both TI (P=0.001) and TE (P<0.001). No significant changes in burst amplitude were observed; however, time‐to‐peak activity (Tpeak/TI) was shifted from 85±2 to 72±5% (P<0.01). Perfusion with MEQ also produced a small increase in HFO spectral power (P=0.07), shifted HFO onset to an earlier time point in the phrenic burst (from 62±3 to 36±7% TI; P<0.01), and prolonged the duration of significant HFO activity. No changes in MFO activity were seen. These data suggest that neuronal gap junctions participate in both the slow and fast oscillatory rhythms underlying phrenic nerve discharge. Supported by NS045321