Functional expression and characterization of histamine-gated chloride channels
- In this thesis we demonstrate for the first time that histamine effectively potentiates GABA-evoked current in heteromultimeric \(GABA_{A}\) receptors. Further it directly opens homomultimeric \(GABA_{A}\) receptors that thus function as histamine-gated channels. A typical 2-4 fold potentiation was found for various combinations of \(GABA_{A}\) receptors expressed in \(\it Xenopus\) oocytes and HEK293 cells. In homomultimeric \(/beta\) channels, histamine opened the channel with a far better efficacy than GABA. A pharmacological characterization in combination with the investigation of mutated \(\beta_{1}\) subunits (M286W) indicates that histamine and propofol acts by similar mechanisms. Histamine is a good candidate for an endogenous ligand acting at an allosteric modulatory site and thus may modulate neuronal events by acting directly on \(GABA_{A}\) receptors. We identified further \(GABA_{A}\) \(\beta\) subunits as potential components of mammalian histamine-gated channels, whose existence has been proposed for many years.
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| Author: | Arunesh SarasGND |
|---|---|
| URN: | urn:nbn:de:hbz:294-18190 |
| Referee: | Hanns HattGND, Hermann LübbertORCiDGND |
| Document Type: | Doctoral Thesis |
| Language: | English |
| Date of Publication (online): | 2007/01/25 |
| Date of first Publication: | 2007/01/25 |
| Publishing Institution: | Ruhr-Universität Bochum, Universitätsbibliothek |
| Granting Institution: | Ruhr-Universität Bochum, International Graduate School of Neuroscience |
| Date of final exam: | 2005/11/24 |
| Creating Corporation: | International Graduate School of Neuroscience |
| GND-Keyword: | GABAA-Rezeptor; Histamin; Chloridkanal; Elektrophysiologie; Voltage-Clamp-Methode |
| Institutes/Facilities: | Lehrstuhl für Zellphysiologie |
| Dewey Decimal Classification: | Naturwissenschaften und Mathematik / Biowissenschaften, Biologie, Biochemie |
| faculties: | International Graduate School of Neuroscience (IGSN) |
| Licence (German): |  Keine Creative Commons Lizenz - es gelten der Veröffentlichungsvertrag und das deutsche Urheberrecht |
