رسالة جامعية

Ion Channel Modulation by Photocaged Dioctanoyl PIP2

التفاصيل البيبلوغرافية
العنوان: Ion Channel Modulation by Photocaged Dioctanoyl PIP2
المؤلفون: Ha, Junghoon
المصدر: Theses and Dissertations.
بيانات النشر: VCU Scholars Compass.
المجموعة: Virginia Commonwealth University
مصطلحات موضوعية: PIP2, Ion Channel, Life Sciences, Physiology
الوصف: Phosphatidylinositol bisphosphate (PIP2) directly regulates electrophysiological activity in a diverse family of ion channels whether the effect is stimulatory or inhibitory. Much has been unveiled about the apparent affinity and modulatory function of PIP2 using a chemically modified dioctanoyl PIP2 (diC8), a membrane delimited cytosolic co-factor in inside-out macropatch experiments. Yet, the scarcity of molecular tools that permit fine external control in whole-cell systems has precluded future studies from probing the physiological role of PIP2 in cells in the presence of a fully intact cytoplasm. Here we introduce light as an external control for PIP2 through photocaging of diC8, and test its activation of Kir2.3 (IRK3), an inwardly rectifying ion channel that has previously shown to possess moderate binding affinity to PIP2, in excised, inside-out macropatches. Our experiments revealed that photocaged-diC8 and irradiated photocaged-diC8 have significantly different activation kinetics than the fully active diC8. Surprisingly, the activation of caged-diC8 by UV irradiation attenuated Kir2.3 activity, while the inactivated diC8 (caged-diC8) resulted in similar magnitude of channel activity compared to the currents elicited by unmodified diC8. Interestingly, we also show that application of both activated (irradiated) and inactive (caged) diC8 in macropatches generated highly fluctuating ion channel activity.
Original Identifier: oai:scholarscompass.vcu.edu:etd-2929
نوع الوثيقة: text
وصف الملف: application/pdf
الإتاحة: http://scholarscompass.vcu.edu/etd/1930Test
http://scholarscompass.vcu.edu/cgi/viewcontent.cgi?article=2929&context=etdTest
حقوق: © The Author
رقم الانضمام: edsndl.vcu.edu.oai.scholarscompass.vcu.edu.etd.2929
قاعدة البيانات: Networked Digital Library of Theses & Dissertations