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A Novel pH Conditioned Cl‐ Conductance in Nodose Ganglia Neurons
Author(s) -
Wang Runping,
Whiteis Carol A.,
Benson Christopher J.,
Chapleau Mark W.,
Abboud François M.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.892.7
Subject(s) - chemistry , reversal potential , niflumic acid , extracellular , biophysics , conductance , depolarization , nodose ganglion , intracellular ph , patch clamp , membrane potential , anesthesia , medicine , endocrinology , vagus nerve , biochemistry , receptor , biology , mathematics , combinatorics , stimulation
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 Ca 2+ 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 Ca 2+ 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).