Blockade of Na+/H+ exchange enhances phrenic burst frequency under control conditions but not in response to hypercapnia in arterially‐perfused adult rat

Abstract

Increased levels of CO2 (hypercapnic acidosis, HA) produce a marked increase in ventilation. Numerous studies have suggested that this hypercapnia‐induced respiratory excitation results from the fall in intracellular pH (pHi), and that Na+/H+ exchange (NHE) plays an important role in regulating pHi recovery during HA. In CO2 chemosensitive respiratory neurons, however, pHi recovery is not observed during HA. The current study was therefore undertaken to determine the role of NHE in respiratory activity under control conditions and in response to HA. To address this issue, we examined phrenic nerve discharge in response to increasing CO2 from 5% to 10% in an arterially‐perfused adult rat preparation (n=5) under control conditions and during NHE blockade using dimethyl‐amiloride hydrochloride (DMA, 283 µM). Under control conditions, HA increased burst frequency by ~34% (P<0.01) due to a marked reduction in TE (~25%, P<0.01) and a small decrease in TI (~15%, P=0.1). Perfusion with DMA elicited a robust increase in burst frequency of ~65% (P<0.001) due solely to a reduction in TE (P<0.001). Under these conditions, burst frequency was not further altered by HA (P=0.2) although TI was still decreased by ~15% (P<0.05). These results indicate that interference with pHi regulation is capable of enhancing phrenic burst frequency under control conditions but is ineffective in altering burst frequency during HA. Supported by NS045321