Role of intracellular and extracellular pH in the chemosensitive response of rat locus coeruleus neurones

Jessica Andrea Filosa, J. B. Dean, R. W. Putnam

Research output: Contribution to journalArticle

110 Citations (Scopus)

Abstract

The chemosensitive response of locus coeruleus (LC) neurones to changes in intracellular pH (pHi), extracellular pH (pHo) 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 pHi and membrane potential (Vm). Hypercapnic acidosis (15% CO21, pHo 6.8) resulted in a maintained fall in pHi 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-, pHo 7.45) resulted in a smaller and transient fall in pHi 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 (pHo 6.8) resulted in a progressive fall in pHi 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-, pHo 7.45) resulted in a transient fall in pHi of 0.18 pH units but little increase in firing rate. Isocapnic acidosis (5% CO2, 7 mM HCO36-, pHo 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 pHi preceded or occurred simultaneously with the changes in firing rate and were considerably slower than the changes in pHo. 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 pHi, indicating that a decrease in pHi is a major part of the intracellular signalling pathway that transduces an acid challenge into an increased firing rate in LC neurones.

Original languageEnglish (US)
Pages (from-to)493-509
Number of pages17
JournalJournal of Physiology
Volume541
Issue number2
DOIs
StatePublished - Jun 1 2002

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Locus Coeruleus
Neurons
Acidosis
Acids
Hypercapnia
Optical Imaging
Propionates
Fluorescence Microscopy
Membrane Potentials
Brain Stem

ASJC Scopus subject areas

  • Physiology

Cite this

Role of intracellular and extracellular pH in the chemosensitive response of rat locus coeruleus neurones. / Filosa, Jessica Andrea; Dean, J. B.; Putnam, R. W.

In: Journal of Physiology, Vol. 541, No. 2, 01.06.2002, p. 493-509.

Research output: Contribution to journalArticle

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abstract = "The chemosensitive response of locus coeruleus (LC) neurones to changes in intracellular pH (pHi), extracellular pH (pHo) 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 pHi and membrane potential (Vm). Hypercapnic acidosis (15{\%} CO21, pHo 6.8) resulted in a maintained fall in pHi 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-, pHo 7.45) resulted in a smaller and transient fall in pHi 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 (pHo 6.8) resulted in a progressive fall in pHi 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-, pHo 7.45) resulted in a transient fall in pHi of 0.18 pH units but little increase in firing rate. Isocapnic acidosis (5{\%} CO2, 7 mM HCO36-, pHo 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 pHi preceded or occurred simultaneously with the changes in firing rate and were considerably slower than the changes in pHo. 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 pHi, indicating that a decrease in pHi is a major part of the intracellular signalling pathway that transduces an acid challenge into an increased firing rate in LC neurones.",
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