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Master of Science (MS)
Serrano-Moreno, José Ramón
Rose, Jacqueline K.
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.
Western Washington University
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Fuqua, Margaret A., "Voltage-sensitive gating of the Pannexin-1 channel" (2013). WWU Masters Thesis Collection. 393.