Optical probing of acetylcholine receptors on neurons in the medial habenula with a novel caged nicotine drug analogue
| Autor: | Graham C. R. Ellis-Davies, Matthew T. Richers, Ek Raj Thapaliya, Zuxin Chen, Stefan Passlick |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Agonist Physiology Chemistry medicine.drug_class Nicotine 03 medical and health sciences Nicotinic acetylcholine receptor 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure nervous system medicine Biophysics Soma Medial habenula Receptor 030217 neurology & neurosurgery Acetylcholine Acetylcholine receptor medicine.drug |
| Zdroj: | The Journal of Physiology. 596:5307-5318 |
| ISSN: | 0022-3751 |
| DOI: | 10.1113/jp276615 |
| Popis: | Key points A new caged nicotinic acetylcholine receptor (nAChR) agonist was developed, ABT594, which is photolysed by one- and two-photon excitation. The caged compound is photolysed with a quantum yield of 0.20. One-photon uncaging of ABT594 elicited large currents and Ca2+ transients at the soma and dendrites of medial habenula (MHb) neurons of mouse brain slices. Unexpectedly, uncaging of ABT594 also revealed highly Ca2+ -permeable nAChRs on axons of MHb neurons. Abstract Photochemical release of neurotransmitters has been instrumental in the study of their underlying receptors, with acetylcholine being the exception due to its inaccessibility to photochemical protection. We caged a nicotinic acetylcholine receptor (nAChR) agonist, ABT594, via its secondary amine functionality. Effective photolysis could be carried out using either one- or two-photon excitation. Brief flashes (0.5-3.0 ms) of 410 nm light evoked large currents and Ca2+ transients on cell bodies and dendrites of medial habenula (MHb) neurons. Unexpectedly, photorelease of ABT594 also revealed nAChR-mediated Ca2+ signals along the axons of MHb neurons. |
| Databáze: | OpenAIRE |
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