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Department of Molecular Physiology

Our interests

olfaction
Introduction



Anholt, R.R (1987) Trends in Biochemical Science 12:58

Frings, S. (2001) Cellular and Molecular Life Sciences 58:510

Olfactory sensory neurons (OSNs) are specialized cells that detect odorants in the inhaled air and produce an electrical signal that supplies the brain with information about the chemical nature and the concentration of the odorants. The process of turning a chemical signal into an electrical signal is called chemo-electrical signal transduction. It involves a set of transduction molecules - receptors, enzymes, ion channels - all located within the sensory cilia of OSNs. On the left figure you can see the sensory cilia protruding from the olfactory epithelium into the nasal cavity where they operate as very efficient chemosensors.

We are interested to find out more about what happens when the cilia detect odorants. Research in many labs has yielded a concept of signal trandsuction which nis illustrated in the right figure. The cilia possess odorant receptor proteins (R) which bind odorants and start the whole process. Although the genome of mammals has several hundreds of different genes for odorant receptors, only one of them is expressed in each OSN, thus giving the cell odorant selectivity. Upon binding an odorant, the receptor turns on adenylyl cyclase (AC), a membrane protein that synthesizes cAMP, the second messenger of olfactory transduction.

To turn this chemical message into an electrical signal, OSNs employ an unusual way of generating a receptor current. First, cAMP opens cation channels that allows Na and Ca ions to enter the cilia. Then, the inflowing Ca opens Cl channels which are much more abundant than the cation channels. Consequently, a strong Cl efflux depolarizes the cells and causes electrical excitation.

Our work is focussed on these two types of ion channels. We try to find out how they together cause depolarization and electrical excitation of the OSN. We examine how the channels are activated by cAMP, how they are inhibited by calmodulin (CaM), and which role the intracellular Ca concentration plays in olfactory signal transduction.



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