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Updated: Jun 28, 2026

Evaluation of Synaptic Multiplicity Using Whole-cell Patch-clamp Electrophysiology
Published on: April 23, 2019
Calcium-sensing receptor activation depresses synaptic transmission
Cecilia G Phillips1, Mark T Harnett, Wenyan Chen
1Division of Pulmonary & Critical Care Medicine, Oregon Health & Science University, Portland, Oregon 97239, USA.
The extracellular calcium sensing receptor (CaSR) regulates synaptic transmission. Reduced CaSR function enhances neurotransmission, while CaSR activation inhibits it, potentially by modulating calcium levels.
Area of Science:
- Neuroscience
- Neurophysiology
- Molecular Biology
Background:
- Neuronal activity affects extracellular calcium ([Ca](o)) and synaptic transmission.
- Activity-dependent calcium influx reduces synaptic release probability.
- The extracellular calcium sensing receptor (CaSR) is present on cortical nerve terminals.
Purpose of the Study:
- To investigate the role of CaSR in modulating synaptic transmission.
- To determine if CaSR activation can influence neurotransmission during changes in extracellular calcium.
Main Methods:
- Patch-clamp recordings from isolated cortical terminals, neuronal pairs, and neuronal soma.
- Utilized reduced affinity CaSR-mutant (CaSR(-/-)) neurons and wild-type controls.
- Applied CaSR agonist spermidine to assess its effects on synaptic transmission.
Main Results:
- CaSR(-/-) neurons exhibited an 88% increase in excitatory postsynaptic currents (EPSCs) compared to wild-type.
- Enhanced transmission in CaSR(-/-) neurons was attributed to increased release probability, not quantal size or release sites.
- Spermidine reduced synaptic transmission and increased paired-pulse depression, acting presynaptically without affecting voltage-gated calcium channels.
Conclusions:
- CaSR plays a significant role in modulating synaptic transmission.
- Reduced CaSR function enhances neurotransmission by increasing release probability.
- CaSR activation can counteract the effects of decreased extracellular calcium on synaptic release.
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