Theses and Dissertations from UMD

Permanent URI for this communityhttp://hdl.handle.net/1903/2

New submissions to the thesis/dissertation collections are added automatically as they are received from the Graduate School. Currently, the Graduate School deposits all theses and dissertations from a given semester after the official graduation date. This means that there may be up to a 4 month delay in the appearance of a give thesis/dissertation in DRUM

More information is available at Theses and Dissertations at University of Maryland Libraries.

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2007 - 200912010 - 20151

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    Role of BK channels in cardiac function
    (2015) Lai, Michael; Meredith, Andrea L; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    Large-conductance voltage- and Ca2+-activated potassium (BK) channels are critical modulators of cellular excitability throughout the cardiovascular and nervous systems. The first aim of this work focuses on a novel role for BK channels in regulating cardiac pacing. Recently, BK channels were implicated in heart rate regulation, but the underlying mechanism was unclear. We hypothesized that BK channels regulate heart rate by modulating the intrinsic excitability of sinoatrial node cells (SANCs), the predominant cardiac pacemaking cells. We found that BK channel protein was expressed in SANCs, and that elimination of BK currents via pharmacological inhibition and genetic ablation reduces SANC excitability. Additionally, we characterized the properties of BK currents from SANCs. Our results indicate that BK channels are novel regulators of SANC function, and suggest that BK channels can serve as a novel therapeutic target for treating heart rate disorders. The second aim of this work focuses on the effect of single-nucleotide polymorphisms (SNPs) on BK current properties. There are approximately 100 known non-synonymous SNPs in human KCNMA1, the gene that encodes BK channels, but few have been characterized or linked with disease. We hypothesized that SNPs in KCNMA1 associated with disease, or located in domains of the BK channel gating ring that mediate Ca2+-dependent activation would alter BK current properties. We determined that the effects of SNPs on BK current properties were Ca2+ concentration-dependent. Also, we found that SNP-induced alterations in current kinetics influenced the amplitude of BK currents evoked by action potential waveforms. These results indicate that SNPs in KCNMA1 can modulate BK current properties and could contribute to the diversity of BK currents evoked by physiological stimuli.
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    Development and Testing of a Metabolic Workload Measurement System for Space Suits
    (2007-06-05) Koscielniak, Agnieszka; Akin, David L; Aerospace Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    Real time knowledge of the metabolic workload of an astronaut during an Extra-Vehicular Activity (EVA) can be instrumental for space suit research, design, and operation. Three indirect calorimetry approaches were developed to determine the metabolic workload of a subject in an open-loop space suit analogue. A study was conducted to compare the data obtained from three sensors: oxygen, carbon dioxide, and heart rate. Subjects performed treadmill exercise in an enclosed helmet assembly, which simulated the contained environment of a space suit while retaining arm and leg mobility. These results were validated against a standard system used by exercise physiologists. The carbon dioxide sensor method was shown to be the most reliable and a calibrated version of it is recommended for implementation into the MX-2 neutral buoyancy space suit analogue.