Dopaminergic modulation of cultured rat olfactory receptor neurons

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Title Dopaminergic modulation of cultured rat olfactory receptor neurons
Publication Type dissertation
School or College College of Pharmacy
Department Pharmacology & Toxicology
Author Granell, Gricelly Vargas
Date 1999-12
Description The presence of dopamine D 2 receptors in olfactory receptor neurons (ORNs) suggests that odor sensitivity may be modulated by neurotransmitters at the level of primary sensory neurons. Because the hyperpolarization-activated, I h , channel is present in ORNs, controls cell excitability and is modulated by dopamine in other systems, I used standard patch-clamp techniques to study the effects of dopamine on I h in cultured rat ORNs. Application of 1 ?M dopamine reversibly shifted I h activation to more negative potentials and decreased I h , maximal relative conductance. Sulpiride, a dopamine D 2 receptor antagonist, blocked the effects of dopamine; while, quinpirole (selective D 2 agonist) mimicked them. External application of an adenylyl cyclase inhibitor (SQ 22536) produced a reversible decrease in I h peak currents, but had no effect OR I h voltage dependence of activation. However, internal application of cAMP shifted I h activation to more depolarized potentials. These findings showed that dopamine regulates I h by activation of D 2 receptors and subsequent inhibition of adenylyl cyclase. Whether this modulation resulted from a direct interaction of cAMP with the channel or a phosphorylation-dependent mechanism was unclear. I found that both cAMP (through a direct interaction with the channel) and PKA-mediated phosphorylation regulated the voltage dependence of I h activation. In addition, PKA modulated Ih maximal relative conductance; cAMP had no effect. These results showed that, in rat ORNs, the voltage dependence of I h activation is dually regulated by a direct action of cAMP on the channel and by PKA; while, the maximal conductance is regulated by phosphorylation alone. Since I h contributes to the modulation of cell excitability, these findings suggest a mechanism by which dopaminergic reduction of cAMP levels and the phosphorylation state in ORNs would inhibit I h and thereby alter resting properties as well as modulate odor sensitivity.
Type Text
Publisher University of Utah
Subject Protein Kinase A; Hyperpolarization; Dopaminergic; Offactory Receptor
Subject MESH Pharmacology; Neurology; Protein Kinases
Dissertation Institution University of Utah
Dissertation Name PhD
Language eng
Relation is Version of Digital reproduction of "Dopaminergic modulation of cultured rat olfactory receptor neurons." Spencer S. Eccles Health Sciences Library. Print version of "Dopaminergic modulation of cultured rat olfactory receptor neurons." available at J. Willard Marriott Library Special Collection. QP6.5 1999 .G72.
Rights Management © Gricelly Vargas Granell.
Format application/pdf
Format Medium application/pdf
Format Extent 2,558,757 bytes
Identifier undthes,5211
Source Original: University of Utah Spencer S. Eccles Health Sciences Library (no longer available).
Master File Extent 2,558,798 bytes
ARK ark:/87278/s63x88ht
Setname ir_etd
ID 191589
Reference URL https://collections.lib.utah.edu/ark:/87278/s63x88ht
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