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Date Permissions Signed

5-10-2013

Date of Award

2013

Document Type

Masters Thesis

Degree Name

Master of Science (MS)

Department

Biology

First Advisor

Serrano-Moreno, José Ramón

Second Advisor

Otto, Joann

Third Advisor

Rose, Jacqueline K.

Abstract

Since its discovery just over a decade ago, Pannexin-1 (Px1) has been recognized in a number of important physiological and pathophysiological processes such as taste, inflammation, and tumor suppression. This large-pore, polymodal ion channel was initially identified as ‗voltage-dependent,‘ though there have been no precise studies concerning the gating properties of Px1 to date. Because Px1 is expressed in excitable cells, identifying voltage-gating properties of Px1 was our primary goal. Using the two-electrode voltage clamp technique, we showed for the first time that Px1 is a weakly voltage-gated channel. Depolarizing voltages up to +200 mV revealed half-maximal activation at +51 mV and a weak voltage-dependence through generation of a complete Boltzmann activation curve. We also showed that Px1 activates in < 3.5 ms, consistent with the time frame of action potentials (1-4 ms). Opening rates of Px1 also seemed to be very weakly voltage-dependent. Further, we showed that Px1 displays consistent current decay at depolarizing voltages greater than +100 mV. Additionally, using two cell systems to exogenously express Px1, we observed a marked decrease of functional Px1 expression within ~24 hours of injection. Taken together, our findings suggest that Px1 is a fast opening, voltage-sensitive channel that may have a number of mechanisms in place to prevent uncontrolled conductivity.

Type

Text

DOI

https://doi.org/10.25710/e0b7-wf13

Publisher

Western Washington University

OCLC Number

849649786

Subject – LCSH

Gap junctions (Cell biology)--Electric properties; Ion channels--Electric properties; Tumor suppressor proteins--Electric properties

Format

application/pdf

Genre/Form

masters theses

Language

English

Rights

Copying of this document in whole or in part is allowable only for scholarly purposes. It is understood, however, that any copying or publication of this thesis for commercial purposes, or for financial gain, shall not be allowed without the author's written permission.

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