- Restrictions on Access:
- Open Access.
- The Axon Initial Segment (AIS) Region of mammalian sensory neurons behaves as the locus of action potential generation and compartmentalizes polar neurons into distinct regions. Voltage-gated potassium ion channels of the EAG superfamily concentrate to the AIS, aiding in the regulation of neuronal excitability. The Elk potassium ion channel subfamily exhibits activity when other voltage-gated channels tend to be closed, suggesting a central role in resting potential modulation. Here, we discuss the presence and role of structural components in the AIS and their relation to Elk. Additionally, a methodological approach to fitting Elk1 G-V curves is developed. This method allows us to consider the mechanisms involved in channel opening and closing. The modulation of local pH and heme concentration influences the gating kinetics of these channels, and the additional presence of heme contributes to a left shifted component of the G-V curve, while a control component comprises the remaining parts of the curve. The HXXXC motif and its involvement in hematin binding is explored through the study of H368Q and C372A mutants. This motif plays a key role in hematin binding in human Elk1 channels, and is shown to generate changes in hematin affinity in mutated channels. A kinetic model for the gating of Elk potassium ion channels is proposed. This model expands upon the understanding of neuronal action potential generation and propagation in the AIS of polar sensory neurons.
- Dissertation Note:
- B.S. Pennsylvania State University 2020.
- Technical Details:
- The full text of the dissertation is available as an Adobe Acrobat .pdf file ; Adobe Acrobat Reader required to view the file.
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