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Published on: May 25, 2011
Distinct Calcium Sources Support Multiple Modes of Synaptic Release from Cranial Sensory Afferents
Jessica A Fawley1, Mackenzie E Hofmann2, Michael C Andresen2
1Department of Physiology and Pharmacology, Oregon Health & Science University, Portland, Oregon 97239 fawley.jessica@gmail.com.
Calcium entry via voltage-activated calcium channels (CaV) and TRP Vanilloid 1 (TRPV1) receptors differentially regulates neurotransmission. Asynchronous release relies on CaV, not TRPV1, indicating distinct release mechanisms for vesicle pools.
Area of Science:
- Neuroscience
- Synaptic transmission
- Ion channel function
Background:
- Craniosensory afferents utilize TRP Vanilloid 1 (TRPV1) receptors and voltage-activated calcium channels (CaV) for neurotransmission.
- Synaptic release is characterized by synchronous, asynchronous, spontaneous, and thermally gated modes.
Purpose of the Study:
- To investigate the calcium sources (CaV and TRPV1) regulating different modes of neurotransmitter release at the solitary tract nucleus (NTS).
- To determine if calcium sourced from CaV or TRPV1 differentially impacts synchronous, asynchronous, spontaneous, and thermally evoked release.
Main Methods:
- Used rat brainstem slices and solitary tract (ST) stimulation.
- Blocked CaV channels with Cd(2+) or ω-conotoxin GVIA.
- Activated TRPV1 with resiniferatoxin or temperature.
- Buffered intracellular calcium using EGTA-AM or BAPTA-AM.
Main Results:
- CaV blockers reduced synchronous and asynchronous EPSCs but not spontaneous or thermal release.
- TRPV1 activation increased spontaneous release rates but did not affect synchronous or asynchronous release.
- Intracellular calcium buffering preferentially reduced asynchronous release.
- Asynchronous release is dependent on CaV, not TRPV1, suggesting separate release mechanisms.
Conclusions:
- Calcium entry through CaV and TRPV1 sources are functionally segregated, regulating distinct vesicle release mechanisms.
- Asynchronous release is a distinct marker of unmyelinated afferents, regulated by CaV.
- Separate vesicle pools with unique calcium sensors and spatial domains underlie different release modes, offering novel targets for synaptic modulation.
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