Modelling and sensitivity analysis of the reactions involving receptor, G-protein and effector in vertebrate olfactory receptor neurons.
A biochemical model of the receptor, G-protein and effector (RGE) interactions during transduction in the cilia of vertebrate olfactory receptor neurons (ORNs) was developed and calibrated to experimental recordings of cAMP levels and the receptor current (RC). The model describes the steps from odorant binding to activation of the effector enzyme which catalyzes the conversion of ATP to cAMP, and shows how odorant stimulation is amplified and delayed by the RGE transduction cascade. A time-dependent sensitivity analysis was performed on the model. The model output-the cAMP production rate-is particularly sensitive to a few, dominant parameters. During odorant stimulation it depends mainly on the initial density of G-proteins and the catalytic constant for cAMP production.
Halnes
Geir
G
School of Computer Science and Communication, Royal Institute of Technology, AlbaNova University Center, 106 91 Stockholm, Sweden. geirh@kth.se
Ulfhielm
Erik
E
Eklöf Ljunggren
Emma
E
Kotaleski
Jeanette Hellgren
JH
Rospars
Jean-Pierre
JP
D000818:Animals; D001703:Biophysics / Q000379:methods; D002923:Cilia / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D019204:GTP-Binding Proteins / Q000378:metabolism*; D007313:Insecta; D008959:Models, Neurological; D009812:Odorants; D018034:Olfactory Receptor Neurons / Q000502:physiology*; D010812:Physical Stimulation / Q000379:methods; D012680:Sensitivity and Specificity; D015398:Signal Transduction / Q000502:physiology*; D013268:Stimulation, Chemical
D000242:Cyclic AMP; D019204:GTP-Binding Proteins