Montgomery, JohannaAshton, JesseArgent, LiamSmith, Joscelin2022-08-022022-08-022022https://hdl.handle.net/2292/60639Atrial fibrillation (AF) is the most common type of cardiac arrhythmia. It is associated with severe co-morbidities and is characterised by rapid, irregular atrial contractions. Treatment for AF can be challenging: pulmonary vein isolation (PVI) surgery is commonly used for AF, but success rates drop with time. Patient outcomes are improved when PVI is combined with ablation of the Ganglionated Plexi (GP), structures important in initiating and maintaining AF. The mechanisms underlying this relationship are unknown. GPs are neuron clusters found on the surface of the heart, which integrate signals from the central nervous system (CNS) and peripheral nervous system (PNS) to control heart rate and rhythm. This thesis aims to examine changes that occur in the GP with AF, focusing on neuron excitability and plasticity due to their likely role in AF generation. Immunohistochemistry, whole-cell patch clamping and a novel method of calcium imaging in an intact atrial GP preparation were used to compare the responses of spontaneously hypertensive rats (SHRs), which are particularly susceptible to AF, to Wistar-Kyoto (WKY) controls. SHR GP neurons showed increased excitability: they exhibited a depolarised resting membrane potential (RMP), lower rheobase, lower action potential (AP) threshold and greater spontaneous excitatory postsynaptic current (sEPSC) amplitude. Additionally, evoked cholinergic intracellular calcium responses were larger in SHR GP neurons, again indicating increased neuron excitability. Multiple GP neuron subtypes were identified electrophysiologically, and SHRs showed a higher proportion of neurons with fast after hyperpolarisations (AHPs), which will likely affect GP function. Glutamatergic receptors, central to plasticity in the brain, were examined to determine if they contribute to changes in GP excitability. GP neurons did not respond to the co-application of glutamate and glycine, suggesting glutamate receptors do not contribute to synaptic transmission or plasticity in the GP. Together, the data in this thesis reveal significant differences in excitability, neuron heterogeneity, membrane function, and synaptic transmission in WKY and SHR GPs. Given the higher propensity of SHRs for AF and the known role of the GP in initiating and maintaining AF, these cellular changes may contribute to AF mechanisms. These data improve our understanding of GP neurons, which will aid the future development and refinement of AF therapies.Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated.https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htmhttp://creativecommons.org/licenses/by-nc-sa/3.0/nz/Thesis2022-06-28Copyright: The authorhttp://purl.org/eprint/accessRights/OpenAccess