| LDR | | 00000nam u2200205 4500 |
| 001 | | 000000433024 |
| 005 | | 20200225111248 |
| 008 | | 200131s2019 ||||||||||||||||| ||eng d |
| 020 | |
▼a 9781085749497 |
| 035 | |
▼a (MiAaPQ)AAI22617684 |
| 040 | |
▼a MiAaPQ
▼c MiAaPQ
▼d 247004 |
| 082 | 0 |
▼a 616 |
| 100 | 1 |
▼a DeBoeuf, Kristi Summers. |
| 245 | 14 |
▼a The Suppressive Effects of Amyloid Beta Fragments (1-42) and (25-35) on Macro- and Micro-Scopic KV1.1 Currents Expressed in Xenopus oocytes. |
| 260 | |
▼a [S.l.]:
▼b Indiana University.,
▼c 2019. |
| 260 | 1 |
▼a Ann Arbor:
▼b ProQuest Dissertations & Theses,
▼c 2019. |
| 300 | |
▼a 140 p. |
| 500 | |
▼a Source: Dissertations Abstracts International, Volume: 81-03, Section: B. |
| 500 | |
▼a Advisor: Farley, Joseph. |
| 502 | 1 |
▼a Thesis (Ph.D.)--Indiana University, 2019. |
| 506 | |
▼a This item must not be sold to any third party vendors. |
| 520 | |
▼a The beta amyloid peptide (A棺) has long been a hallmark of Alzheimer's Disease (AD) pathology. Past studies have linked its involvement to the disruption of Ca2+ homeostasis, synaptic communication, and long-term potentiation (LTP), but the underlying mechanism(s) is still largely unclear. Because Kv1.1 and related channels are activated during an action potential, regulate depolarization Ca2+ influx, and the inhibition of Kv1 channels can be neurotoxic, Kv1 channels serve as intriguing A棺 target candidates in early AD pathogenesis. Using murine Kv1.1 channels expressed in Xenopus laevis oocytes, the present dissertation examined the effects of A棺(1-42) and the "core" peptide (25-35) on both macro- and micro-scopic Kv1.1 currents. Early work in the Farley lab has shown that A棺(1-42) suppressed macroscopic Kv1.1 currents ~50%, and the present work has sought to expand upon these results to determine 1) whether the suppression of Kv1.1 by A棺(1-42) could involve direct peptide-peptide interactions using patch clamp and artificial membrane techniques [tip-dip, Black Lipid Membranes (BLMs)], 2) whether the suppression by A棺(1-42) involved the removal of channels from the membrane utilizing membrane capacitance analyses and western blotting methods, and 3) whether A棺(25-35) was sufficient for the suppression of Kv1.1 using two-electrode voltage clamp (TEVC). Collectively, the single channel work presented in this dissertation (patch clamp, tip-dip, BLM) showed that direct application of A棺(1-42) to individual Kv1.1 subunits did reduce channel activity whether applied intra- or extra-cellularly. The TEVC and western blot analyses revealed that the suppression of Kv1.1 by A棺(1-42) did not seem to involve the endocytosis of channels from the membrane. Furthermore, the shorter core fragment, A棺(25-35), did cause suppression of Kv1.1, but did not fully account for the suppression observed by the full-length peptide. Suppression of Kv1.1 and related K+ channels presynaptically could lead to larger and longer action potentials, thus allowing a greater influx of Ca2+ and subsequent increase in glutamate release. Postsynaptically, the increased glutamate release, through activation of AMPA and NMDA receptors, may contribute to excitotoxicity. |
| 590 | |
▼a School code: 0093. |
| 650 | 4 |
▼a Neurosciences. |
| 690 | |
▼a 0317 |
| 710 | 20 |
▼a Indiana University.
▼b Neuroscience. |
| 773 | 0 |
▼t Dissertations Abstracts International
▼g 81-03B. |
| 773 | |
▼t Dissertation Abstract International |
| 790 | |
▼a 0093 |
| 791 | |
▼a Ph.D. |
| 792 | |
▼a 2019 |
| 793 | |
▼a English |
| 856 | 40 |
▼u http://www.riss.kr/pdu/ddodLink.do?id=T15493477
▼n KERIS
▼z 이 자료의 원문은 한국교육학술정보원에서 제공합니다. |
| 980 | |
▼a 202002
▼f 2020 |
| 990 | |
▼a ***1008102 |
| 991 | |
▼a E-BOOK |