Sarah Maria Trattnig

October 2004 – January 2009:
Msc Pharm, Faculty of Life Sciences, University of Vienna, Austria

June 2009:
Ph.d student, Department of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen

Molecular pharmacology studies of the 5-HT₃ receptor and other Cys-loop receptors

Background
The superfamily of ligand-gated ion channels (LGICs) mediate fast synaptic responses. In 2003, a novel member was added to the superfamily, when a human LGIC activated by divalent cations like Zn²⁺ and Cu²⁺, termed the ‘Zn²⁺-Activated Channel’ (ZAC), was discovered (1). The focus of my project is on 5-HT₃ receptors (5-HT₃ Rs) and ZAC., which belong to the Cys loop receptor family within the LGIC.

The 5-HT₃Rs: Serotonin mediates its physiological functions through 7-TM receptors and the 5-HT₃Rs. Antagonists targeting 5-HT₃Rs in the PNS are clinically administered to reduce the nausea/emesis connected with radio- and chemotherapy treatment of cancer patients (2). In the CNS, 5-HT₃Rs mediate the fast synaptic response to serotonin, and presynaptic 5-HT₃Rs regulate the synaptic release of serotonin, dopamine, ACh and GABA (3). Thus, central 5-HT₃R signalling has been proposed to be of importance for several psychiatric disorders (4-5).

The ‘Zinc-Activated Channel’ (ZAC): Very little is known about the physiological functions of ZAC. ZAC genes have been identified in the human, dog and genomes but not in rodents. Transcripts of ZAC have been determined in fetal brain, spinal cord, trachea, stomach and placenta tissue (1). In the brain, ZAC transcripts have been found in thalamus, striatum, hippocampus and dentate gyrus (6).

Project Plan
My PhD project is aimed on elucidating the molecular basis of the signal transduction of 5-HT₃Rs and ZAC, with the emphasis on use of electrophysiological methods.

Main supervisor
Anders A Jensen, Lektor, ph.d.
Departement of Medicinal Chemistry, 
Faculty of Pharmaceutical Sciences, University of Copenhagen

Co-supervisor
Bjarke Abrahamsen, post doc, ph.d.
Departement of Medicinal Chemistry, 
Faculty of Pharmaceutical Sciences, University of Copenhagen

1. Davies, P. A., Wang, W., Hales, T. G., and Kirkness, E. F. (2003) J. Biol. Chem. 278(2), 712-717
2. Aapro, M. (2005) Oncology 69, 97-109
3. Fink, K. B., and Gothert, M. (2007) Pharmacol Rev
4. Giordano, J., and Schultea, T. (2004) Pain Physician 7(1), 141-147
5. Dremencov, E., Weizmann, Y., Kinor, N., Gispan-Herman, I., and Yadid, G. (2006) Curr. Drug Targets 7(2), 165-175
6. Houtani, T., Munemoto, Y., Kase, M., Sakuma, S., Tsutsumi, T., and Sugimoto, T. (2005) Biochem. Biophys. Res. Commun. 335(2), 277-285

The project is financed by the Lundbeck Foundation