A Novel pH Conditioned Cl‐ Conductance in Nodose Ganglia Neurons

Abstract

pH sensitivity has been studied extensively in spinal afferents of dorsal root ganglia neurons but rarely in vagal afferents of nodose ganglia (NG) neurons. Here, we report a large and prolonged inward current evoked following 2 or 3 brief (10s) exposures to low pH (6.0) in 16 of 22 (70%) isolated nodose neurons using whole‐cell patch‐clamp technique. This pH‐conditioned current (pH‐I) reached its peak of 904.3±159.9pA (n=15) at ~5 minutes and returned to baseline within 10–15 minutes. Replacing Ca2+ and Na+ in the extracellular solution with NMDG or intracellular K+ with Cs+ did not significantly decrease the current. However pH‐I was eliminated by using a low Cl− (4mM) pipette solution. The I‐V plot showed a reversal potential of ~0mV with equivalent intra‐and extracellular [Cl]− (133mM) in the absence of permeable cations. Replacing [Cl]o− with aspartate shifted the reversal potential to a more positive voltage. pH‐I was reduced by tamoxifen, an inhibitor of “swell‐activated Cl− current” (SAC), but not by niflumic acid (blocker of the Ca2+ activated Cl− channel). Adding hypoosmotic solution, which activates SAC, did not further increase peak pH‐I. Conversely evoking the pH‐I did not increase the SAC current. Opening of this pH conditioned Cl− conductance may contribute to sustained depolarization of vagal afferents and potentiate a beneficial reflex sympathoinhibition during myocardial and gastrointestinal ischemia/acidosis (NIH‐HL14388).