Extracellular Acidification Modifies Ca2+Fluxes in Rat Brain Synaptosomes

Saadoun, Samira; Lluch, Mónica; Rodríguez‐Álvarez, José; Blanco, Isaac; Rodrı́guez, Ricardo

doi:10.1006/bbrc.1997.7927

Cited by 9 publications

(2 citation statements)

References 31 publications

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“…The reduction in spike amplitude suggests that acidification inhibited the calcium channels expressed in H. aspersa neurons. This is consistent with a considerable literature indicating that calcium channels from a variety of cell types, including snail neurons, are inhibited by H ϩ (9,16,31,(41)(42)(43).…”

Section: Resultssupporting

confidence: 93%

CO₂ chemosensitivity in Helix aspersa: three potassium currents mediate pH-sensitive neuronal spike timing

Denton¹,

McCann²,

Leiter³

2007

American Journal of Physiology-Cell Physiology

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Elevated levels of carbon dioxide increase lung ventilation in Helix aspersa. The hypercapnic response originates from a discrete respiratory chemosensory region in the dorsal subesophageal ganglia that contains CO(2)-sensitive neurons. We tested the hypothesis that pH-dependent inhibition of potassium channels in neurons in this region mediated the chemosensory response to CO(2). Cells isolated from the dorsal subesophageal ganglia retained CO(2) chemosensitivity and exhibited membrane depolarization and/or an increase in input resistance during an acid challenge. Isolated somata expressed two voltage-dependent potassium channels, an A-type and a delayed-rectifier-type channel (I(KA) and I(KDR)). Both conductances were inhibited during hypercapnia. The pattern of voltage dependence indicated that I(KA) was affected by extracellular or intracellular pH, but the activity of I(KDR) was modulated by extracellular pH only. Application of inhibitors of either channel mimicked many of the effects of acidification in isolated cells and neurons in situ. We also detected evidence of a pH-sensitive calcium-activated potassium channel (I(KCa)) in neurons in situ. The results of these studies support the hypothesis that I(KA) initiates the chemosensory response, and I(KDR) and I(KCa) prolong the period of activation of CO(2)-sensitive neurons. Thus multiple potassium channels are inhibited by acidosis, and the combined effect of pH-dependent inhibition of these channels enhances neuronal excitability and mediates CO(2) chemosensory responses in H. aspersa. We did not find a single "chemosensory channel," and the chemosensitive channels that we did find were not unique in any way that we could detect. The protein "machinery" of CO(2) chemosensitivity is probably widespread among neurons, and the selection process whereby a neuron acts or does not act as a respiratory CO(2) chemosensor probably depends on the resting membrane potential and synaptic connectivity.

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Section: Resultssupporting

confidence: 93%

CO₂ chemosensitivity in Helix aspersa: three potassium currents mediate pH-sensitive neuronal spike timing

Denton¹,

McCann²,

Leiter³

2007

American Journal of Physiology-Cell Physiology

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“…Relatively moderate pH o shifts, which are closer to OGR1's functional range than the range for ASICs (Levin andBuck 2015, Wemmie et al 2013), provide additional evidence for this conception. A shift in pH o from 7.4 to 6.8 was found to enhance phosphoinositide hydrolysis in synaptosomes (Saadoun et al 1998), suggesting an induction of phospholipase C activation by G protein-linked OGR1. In support of phospholipase C involvement, we have shown that the effects of external pH were sensitive to the specific inhibitor U73122.…”

Section: Discussionmentioning

confidence: 95%

Calcium release from intracellular stores is involved in mitochondria depolarization after lowering extracellular pH in rat brain synaptosomes

Dubouskaya¹,

Hrynevich²,

Waseem³

et al. 2018

Acta Neurobiologiae Experimentalis

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In the brain, pH can be lowered in both healthy and disease states. Previously, we showed that moderate extracellular acidification (down to pHo 7.0), but not intracellular acidification, leads to mitochondrial depolarization in synaptosomes. This indicates that the plasma membranes of neuronal presynaptic endings have proton receptors that can induce mitochondrial dysfunction when activated. In the present paper we attempt to identify this hypothetical receptor. First, we have demonstrated that lowering pHo to 7.0 does not induce sodium influx as monitored by the fluorescent dye Sodium Green. This fact, in conjunction with the absence of calcium influx in the same conditions-demonstrated previously, excludes ion channels as possible receptors. However, we showed that acidification-induced mitochondrial depolarization is sensitive to thapsigargin-an inhibitor of calcium release from intracellular stores, U73122-an inhibitor of phospholipase C, as well as Cu 2+ and Zn 2+ , which can block the metabotropic proton receptor ovarian cancer G protein-coupled recep tor 1 (OGR1). Furthermore, using fluorescent dye Fluo-3 we have demonstrated that moderate extracellular acidification induces a cytosolic calcium increase. Excess calcium was scavenged by mitochondria (monitored by fluorescent dye Rhod-2). Our results suggest that the metabotropic OGR1 is a hypothetical presynaptic receptor for low pH. Its activation leads to phospholipase C activation and calcium release from the endoplasmic reticulum followed by accumulation in mitochondria, which likely causes a decrease in mitochondrial membrane potential.

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Function and Signaling of the pH-Sensing G Protein-Coupled Receptors in Physiology and Diseases

Dong

Yang

2014

Molecular Genetics of Dysregulated pH Homeostasis

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Extracellular Acidification Modifies Ca2+Fluxes in Rat Brain Synaptosomes

Cited by 9 publications

References 31 publications

CO₂ chemosensitivity in Helix aspersa: three potassium currents mediate pH-sensitive neuronal spike timing

CO₂ chemosensitivity in Helix aspersa: three potassium currents mediate pH-sensitive neuronal spike timing

Calcium release from intracellular stores is involved in mitochondria depolarization after lowering extracellular pH in rat brain synaptosomes

Function and Signaling of the pH-Sensing G Protein-Coupled Receptors in Physiology and Diseases

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Extracellular Acidification Modifies Ca2+Fluxes in Rat Brain Synaptosomes

Cited by 9 publications

References 31 publications

CO2 chemosensitivity in Helix aspersa: three potassium currents mediate pH-sensitive neuronal spike timing

CO2 chemosensitivity in Helix aspersa: three potassium currents mediate pH-sensitive neuronal spike timing

Calcium release from intracellular stores is involved in mitochondria depolarization after lowering extracellular pH in rat brain synaptosomes

Function and Signaling of the pH-Sensing G Protein-Coupled Receptors in Physiology and Diseases

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CO₂ chemosensitivity in Helix aspersa: three potassium currents mediate pH-sensitive neuronal spike timing

CO₂ chemosensitivity in Helix aspersa: three potassium currents mediate pH-sensitive neuronal spike timing