Genetically encoded proton sensors reveal activity-dependent pH changes in neurons
Joseph V Raimondo1, Agnese Irkle, Winnie Wefelmeyer
1Department of Pharmacology, Oxford University Oxford, UK.
Frontiers in Molecular Neuroscience
|June 6, 2012
Summary
Researchers used genetically encoded pH sensors to measure intracellular pH changes during epileptic activity in neurons. This demonstrates a new tool for studying neuronal function and pH regulation in neurological conditions.
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- Hydrogen ion concentration (pH) regulation is crucial for cellular functions, including metabolism and enzymatic activity.
- In the nervous system, pH control impacts neuronal development, synaptic transmission, and network excitability.
- Accurate measurement of pH fluctuations is vital for understanding its role in physiological and pathological conditions.
Purpose of the Study:
- To investigate activity-dependent hydrogen ion fluxes in neurons using genetically encoded pH sensors.
- To demonstrate the utility of specific genetically encoded pH sensors for studying neuronal pH dynamics.
- To explore the role of pH changes in network excitability during epileptiform activity.
Main Methods:
- Combined whole-cell patch clamp electrophysiology with simultaneous two-photon or confocal imaging.
- Utilized three genetically encoded pH sensors: deGFP4, E(2)GFP, and Cl-sensor.
- Quantified the amplitude and time course of intracellular acidic transients in neuronal models of temporal lobe epilepsy.
Main Results:
- Successfully quantified neuronal, intracellular, acidic transients evoked by epileptiform activity.
- Demonstrated the suitability of deGFP4, E(2)GFP, and Cl-sensor for measuring activity-dependent pH changes.
- Showcased the application of these sensors in in vitro models of temporal lobe epilepsy.
Conclusions:
- Genetically encoded pH sensors are effective tools for investigating activity-dependent pH changes in single neurons.
- These sensors offer a novel approach to study hydrogen ion fluxes associated with network activity.
- The findings highlight the potential of these sensors in understanding pH dynamics in neurological disorders.
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