Role of Intracellular and Extracellular pH in the Chemosensitive Response of Rat Locus Coeruleus Neurones

Authors

Jessica A. FilosaFollow
Jay B. Dean
Robert W. Putnam, Wright State University - Main CampusFollow

Document Type

Article

Publication Date

6-1-2002

Abstract

The chemosensitive response of locus coeruleus (LC) neurones to changes in intracellular pH (pH_i), extracellular pH (pH_o) and molecular CO₂ were investigated using neonatal rat brainstem slices. A new technique was developed that involves the use of perforated patch recordings in combination with fluorescence imaging microscopy to simultaneously measure pH_i and membrane potential (V_m). Hypercapnic acidosis (15 % CO₂, pH_o 6.8) resulted in a maintained fall in pH_i of 0.31 pH units and a 93 % increase in the firing rate of LC neurones. On the other hand, isohydric hypercapnia (15 % CO₂, 77 mm HCO₃⁻, pH_o 7.45) resulted in a smaller and transient fall in pH_i of about 0.17 pH units and an increase in firing rate of 76 %. Acidified Hepes (N-2-hydroxyethylpiperazine-N′-2- ethanesulfonic acid)-buffered medium (pH_o 6.8) resulted in a progressive fall in pH_i of over 0.43 pH units and an increase in firing rate of 126 %. Isosmotic addition of 50 mm propionate to the standard HCO₃⁻-buffered medium (5 % CO₂, 26 mm HCO₃⁻, pH_o 7.45) resulted in a transient fall in pH_i of 0.18 pH units but little increase in firing rate. Isocapnic acidosis (5 % CO₂, 7 mm HCO₃⁻, pH_o 6.8) resulted in a slow intracellular acidification to a maximum fall of about 0.26 pH units and a 72 % increase in firing rate. For all treatments, the changes in pH_i preceded or occurred simultaneously with the changes in firing rate and were considerably slower than the changes in pH_o. In conclusion, an increased firing rate of LC neurones in response to acid challenges was best correlated with the magnitude and the rate of fall in pH_i, indicating that a decrease in pH_i is a major part of the intracellular signalling pathway that transduces an acid challenge into an increased firing rate in LC neurones.

Repository Citation

Filosa, J. A., Dean, J. B., & Putnam, R. W. (2002). Role of Intracellular and Extracellular pH in the Chemosensitive Response of Rat Locus Coeruleus Neurones. The Journal of Physiology, 541 (2), 493-509.
https://corescholar.libraries.wright.edu/ncbp/171

DOI

10.1113/jphysiol.2001.014142