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ucin1136913935.pdf (1.11 MB)
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CLUSTERING OF CYCLIC-NUCLEOTIDE-GATED CHANNELS IN OLFACTORY CILIA
Author Info
FLANNERY, RICHARD JOHN
Permalink:
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1136913935
Abstract Details
Year and Degree
2006, PhD, University of Cincinnati, Medicine : Neuroscience/Medical Science Scholars Interdisiplinary.
Abstract
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.
Committee
Dr. Steven Kleene (Advisor)
Pages
98 p.
Keywords
olfactory
;
patch-clamp
;
electrophysiology
;
computational modeling
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Citations
FLANNERY, R. J. (2006).
CLUSTERING OF CYCLIC-NUCLEOTIDE-GATED CHANNELS IN OLFACTORY CILIA
[Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1136913935
APA Style (7th edition)
FLANNERY, RICHARD.
CLUSTERING OF CYCLIC-NUCLEOTIDE-GATED CHANNELS IN OLFACTORY CILIA.
2006. University of Cincinnati, Doctoral dissertation.
OhioLINK Electronic Theses and Dissertations Center
, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1136913935.
MLA Style (8th edition)
FLANNERY, RICHARD. "CLUSTERING OF CYCLIC-NUCLEOTIDE-GATED CHANNELS IN OLFACTORY CILIA." Doctoral dissertation, University of Cincinnati, 2006. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1136913935
Chicago Manual of Style (17th edition)
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Document number:
ucin1136913935
Download Count:
814
Copyright Info
© 2005, all rights reserved.
This open access ETD is published by University of Cincinnati and OhioLINK.