DOI
https://doi.org/10.25772/0D50-VM04
Defense Date
1998
Document Type
Thesis
Degree Name
Master of Science
Department
Pharmacology & Toxicology
First Advisor
Leslie S. Satin
Abstract
The objective of this thesis was to understand the regulation of islet Cl⁻ current by cAMP. This current, known as Icl,islet flew is the first Cl⁻ channel current characterized in pancreatic �� cells. Icl,islet has been hypothesized to modulate insulin secretion through changes in islet electrical activity. Both 5 ��M forskolin and 100 ��M IBMX (3-isobutyl-1-methylxanthine), agents that increase intracellular cAMP, were shown to activate an outwardly-rectifying ionic current in HIT cells that closely resembled Icl,islet. The current was blocked when iodide was substituted for external Cl⁻ or when the Cl⁻ channel blocker niflumic acid was applied to cells. In contrast, removal of [Na⁺]O did not inhibit the current. In many cells, Cl⁻ current activated and then spontaneously deactivated following cAMP stimulation, suggesting the possibility that the channel desensitizes to [cAMP]i. Exposing cells to multiple cAMP activators revealed that Cl⁻ current declined because it became refractory to increased [cAMP]i. The implication of these results to islet physiology is discussed.
Rights
© The Author
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
10-17-2018
Comments
Scanned, with permission from the author, from the original print version, which resides in University Archives.