ArticleThe Journal of physiology2013
Genetically encoded pH-indicators reveal activity-dependent cytosolic acidification of Drosophila motor nerve termini in vivo.
Article in The Journal of physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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27 citing papers in PubMed, 48 citations in OpenAlex.
- Optimal neuromuscular performance requires motor neuron phosphagen kinases.The Journal of physiology · 2026Article
- Imaging of mitochondrial matrix pH dynamics reveals a functional interaction between the ADP/ATP carrier and ATP synthase to regulate HPharmacological research · 2025Article
- XPRESSO: Rapid genetic engineering of human pluripotent stem cells for durable overexpression using a modular anti-silencing vector.Stem cell reports · 2025Article
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- Epilepsy insights revealed by intravital functional optical imaging.Frontiers in neurology · 2024Review
- Mitochondrial phosphagen kinases support the volatile power demands of motor nerve terminals.The Journal of physiology · 2023Article
- Loss of Activity-Induced Mitochondrial ATP Production Underlies the Synaptic Defects in aThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Neuronal Glutamatergic Synaptic Clefts Alkalinize Rather Than Acidify during Neurotransmission.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
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- Acid-Base Basics.Seminars in nephrology · 2019Review
- The application of 'kisser' probes for resolving the distribution and microenvironment of membrane proteins in situ.Journal of neurogenetics · 2018Article
- Imaging pH Dynamics Simultaneously in Two Cellular Compartments Using a Ratiometric pH-Sensitive Mutant of mCherry.ACS omega · 2018Article
- A superfolder variant of pH-sensitive pHluorin for in vivo pH measurements in the endoplasmic reticulum.Scientific reports · 2018Article
- KCC2-dependent Steady-state Intracellular Chloride Concentration and pH in Cortical Layer 2/3 Neurons of Anesthetized and Awake Mice.Frontiers in cellular neuroscience · 2018Article
- Diverse modes of synaptic signaling, regulation, and plasticity distinguish two classes ofeLife · 2017Article
- Methods for Imaging Intracellular pH of the Follicle Stem Cell Lineage in Live Drosophila Ovarian Tissue.Journal of visualized experiments : JoVE · 2017Article
- Optical Quantification of Intracellular pH in Drosophila melanogaster Malpighian Tubule Epithelia with a Fluorescent Genetically-encoded pH Indicator.Journal of visualized experiments : JoVE · 2017Article
- NaThe Journal of physiology · 2017Article
- Increased intracellular pH is necessary for adult epithelial and embryonic stem cell differentiation.The Journal of cell biology · 2016Article
- Expression of Carbonic Anhydrase I in Motor Neurons and Alterations in ALS.International journal of molecular sciences · 2016Article
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3 authors at 1 institution in 1 country.
Funding
Abstract
All biochemical processes, including those underlying synaptic function and plasticity, are pH sensitive. Cytosolic pH (pH(cyto)) shifts are known to accompany nerve activity in situ, but technological limitations have prevented characterization of such shifts in vivo. Genetically encoded pH-indicators (GEpHIs) allow for tissue-specific in vivo measurement of pH. We expressed three different GEpHIs in the cytosol of Drosophila larval motor neurons and observed substantial presynaptic acidification in nerve termini during nerve stimulation in situ. SuperEcliptic pHluorin was the most useful GEpHI for studying pH(cyto) shifts in this model system. We determined the resting pH of the nerve terminal cytosol to be 7.30 ± 0.02, and observed a decrease of 0.16 ± 0.01 pH units when the axon was stimulated at 40 Hz for 4 s. Realkalinization occurred upon cessation of stimulation with a time course of 20.54 ± 1.05 s (τ). The chemical pH-indicator 2,7-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein corroborated these changes in pH(cyto). Bicarbonate-derived buffering did not contribute to buffering of acid loads from short (≤ 4 s) trains of action potentials but did buffer slow (~60 s) acid loads. The magnitude of cytosolic acid transients correlated with cytosolic Ca(2+) increase upon stimulation, and partial inhibition of the plasma membrane Ca(2+)-ATPase, a Ca(2+)/H(+) exchanger, attenuated pH(cyto) shifts. Repeated stimulus trains mimicking motor patterns generated greater cytosolic acidification (~0.30 pH units). Imaging through the cuticle of intact larvae revealed spontaneous pH(cyto) shifts in presynaptic termini in vivo, similar to those seen in situ during fictive locomotion, indicating that presynaptic pH(cyto) shifts cannot be dismissed as artifacts of ex vivo preparations.
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