Cyclic nucleotide gated (CNG) channels play an important role in mediating sensory signal transduction in olfactory receptor neurons, which takes place primarily in olfactory cilia. The aim of this thesis was to determine the location of these channels along the length of olfactory cilia, by using a combination of patch-clamp experiments and computational modeling.
The patch-clamp technique was used to determine the rate of activation of CNG channels when cAMP diffuses into an excised cilium. This method revealed a delay in the activation of the channels, indicating a low density of ion channels in the proximal segment of the cilium. Rapid activation of the channels following the delay indicated a high-density of channels in part of the distal segment. Patch-clamp experiments also revealed that Na+ does not accumulate in a cilium to an extent that the driving force for Na + is decreased substantially. This also implies that Na+ and Ca2+ do not accumulate in the presence of Ca2+, so the driving force for Na+ and Ca2+ should be maintained during odor signal transduction.
A computational model made predictions about the rate of activation of CNG channels based on specific ion channel density functions. These functions quantitatively describe the channel densities along the cilium length. Modeled density functions revealed that ion channels expressed in a cluster in the distal segment were required to make accurate predictions about the rate of current activation.
Finally, in collaboration with the departments of mathematics and chemical engineering at UC, we developed an inverse model, which systematically converts time-dependent current traces to ion channel density functions. This method also revealed that ion channels are located in clusters in distal segments.
|School:||University of Cincinnati|
|Department:||Neuroscience/Medical Science Scholars Interdisiplinary|
|School Location:||United States -- Ohio|
|Source:||DAI-B 79/10(E), Dissertation Abstracts International|
|Keywords:||Computational modeling, Electrophysiology, Olfactory, Patch-clamp|
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