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AN ABSTRACT OF THE DISSERTATION OF Eric Martin Kratzer for the degree of Doctor of Philosophy in Molecular and Cellular Biology presented on December 3, 2007 Characterization of Acid Sensing Ion Channel (ASIC) in Mouse Olfactory Bulb

Approved: Roger P. Simon, M.D. This study examined the role of acidsensing ion channels (ASICs) in interneuron synaptic modulation. ASICS are ultra fine discriminators of acidic conditions in the neuronal microenvironment. Each ASIC subunit isoform has innate, subtly different electrophysiological properties and tissue distributions. Structurally, ASICs may form homoor heteromeric channels, yielding combinatorial functional properties regarding their sensitivity to the extracellular environment, saturation limits, inactivation profiles, and putative roles in the initiation of neuronal injury. Electrophysiology provides direct biophysical monitoring of channel activity and allows pharmacological isolation and manipulation. Fura-2 imaging allows direct visualization of calcium ion flux into neurons, verifying their calcium gating ability. Molecular verification of ASIC protein composition via western blotting and Immunocytochemistry showed anatomical distribution patterns of ASIC isoform combinations in the mouse olfactory bulb (OFB) tissue, the first documentation. Genetic knockout animals also verified results and internal controls were also utilized. ASIC isoforms combine their functions perform environmental sensing, and modulation of synaptic transmissions during normal and pathological conditions. Copyright by Eric Martin Kratzer © December 3, 2007 All Rights Reserved Characterization of Acid Sensing Ion Channel (ASIC) in Mouse Olfactory Bulb by Eric Martin Kratzer