Dynamic remodeling of the ionic basis of an intrinsic inhibitory response by the phospholipid PIP2

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dc.contributor.advisorTurner, Ray W.
dc.contributor.authorNicholls, Shane
dc.contributor.committeememberZamponi, Gerald W.
dc.contributor.committeememberAltier, Christophe
dc.date2020-11
dc.date.accessioned2020-09-25T18:33:02Z
dc.date.available2020-09-25T18:33:02Z
dc.date.issued2020-09-22
dc.description.abstractThe excitability of an individual neuron can be directly related to the different types of potassium channels it expresses. Potassium channels that are activated by either calcium or voltage contribute to a wide range of physiological processes and many cognitive impairments if mutated or disrupted. A key mechanism to regulate neuronal activity is to generate afterhyperpolarizations (AHPs). AHPs are brief inhibitory periods that span from a fast (ms) to slow (sec) time frame. A voltage and calcium-gated potassium channel (Kv7) and an intermediate conductance calcium-gated potassium channel (IK) in CA1 hippocampal pyramidal cells hyperpolarize the cell by generating a medium and slow AHP. The availability of at least Kv7 channels can be modulated by a phosphatidylinositol molecule (PIP2). We measured the relative activity of each potassium channel using whole-cell patch recordings in rat hippocampal tissue slices maintained in vitro and in the tsA-201 heterologous expression system. Both channels prove to be activated by calcium increases derived from a combination of Cav1.3 channels and ryanodine receptor 2. However, modulating PIP2 levels produced opposite effects on coexpressed Kv7.2/3 and IK-mediated outward currents. Super resolution microscopy of immunolabeled proteins in cultured hippocampal neurons revealed a novel close association between Kv7.2 and IK potassium channels in somatic and dendritic membranes. The ability for PIP2 to reverse the roles of Kv7.2/3 and IK channels in producing a medium/slow AHP identifies a novel mechanism by which the ionic basis of inhibitory responses can be dynamically modulated to control intrinsic excitability in CA1 pyramidal cells.en_US
dc.identifier.citationNicholls, S. (2020). Dynamic remodeling of the ionic basis of an intrinsic inhibitory response by the phospholipid PIP2 (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.en_US
dc.identifier.doihttp://dx.doi.org/10.11575/PRISM/38236
dc.identifier.urihttp://hdl.handle.net/1880/112576
dc.publisher.facultyCumming School of Medicineen_US
dc.publisher.institutionUniversity of Calgaryen
dc.rightsUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.en_US
dc.subjectIKCaen_US
dc.subjectKv7en_US
dc.subjectmAHPen_US
dc.subjectsAHPen_US
dc.subjectPIP2en_US
dc.subject.classificationNeuroscienceen_US
dc.titleDynamic remodeling of the ionic basis of an intrinsic inhibitory response by the phospholipid PIP2en_US
dc.typemaster thesisen_US
thesis.degree.disciplineMedicine – Neuroscienceen_US
thesis.degree.grantorUniversity of Calgaryen_US
thesis.degree.nameMaster of Science (MSc)en_US
ucalgary.item.requestcopytrueen_US
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