Doctor of Philosophy
Shoemaker, J. Kevin
What discharge properties are expressed by varying-sized sympathetic action potential (AP) subpopulations active under baseline conditions in humans and what are the governing mechanisms? To address this overall question the microneurographic approach was employed to record multi-unit muscle sympathetic nerve activity (MSNA), after which a continuous wavelet transform exposed APs in the recorded neurogram. Study One examined the role of the paravertebral ganglia on sympathetic neural discharge patterns. Through trimethaphan infusion under baseline conditions, this study revealed ordered de-recruitment of larger to smaller AP clusters, suggesting that the paravertebral ganglia contribute to the distribution of firing probabilities expressed by differently-sized sympathetic APs. However, the smallest APs were resistant to trimethaphan, suggesting non-nicotinic mechanisms contribute to ganglionic neurotransmission of this specific subpopulation of axons. Study Two investigated the synchronization of APs within the cardiac cycle and the role played by the paravertebral ganglia in this process. We observed that under baseline conditions ~30% of total sympathetic APs fired asynchronously between bursts of MSNA and asynchronous discharge frequency was not affected by baroreflex or apneic stress. Thus, asynchronous AP discharge represents a fundamental behaviour within human MSNA. Also, retrospective analysis of asynchronous AP data from Study One demonstrated that non-nicotinic ganglionic mechanisms contributed to some, but not all asynchronous AP discharge. Study Three probed the heterogeneity of baroreflex control over the discharge of AP subpopulations. Under baseline conditions, we found a subpopulation of medium-sized APs to express the greatest baroreflex gain, while the smallest and largest APs exhibited minimal baroreflex regulation. During baroreflex stress imposed by lower body negative pressure, the ii sympathetic system increases total MSNA by resetting baroreflex control of medium APs to higher levels of activity and increasing the gain to facilitate augmented firing along with recruiting a subpopulation of previously silent larger APs. Overall, these studies provide new knowledge regarding the complex discharge patterns expressed by subpopulations of varying-sized sympathetic APs active at baseline, of which some express augmented firing during baroreflex stress. We also provide insight to the baroreflex and ganglionic mechanisms governing the discharge of these AP subpopulations.
Summary for Lay Audience
For humans to survive, blood pressure must be maintained within an optimal range and oxygenated blood flow must be delivered to vital organs such as the brain and the heart. Part of the brain known as the sympathetic nervous system ensures these conditions by sending precise messages along the nerves to communicate with the heart and blood vessels. These messages are made up of electrical signals called action potentials. During periods of stress that change our blood pressure and blood flow ⎯ such as the fall in blood pressure that occurs when we stand ⎯ the brain changes the message sent to the heart and blood vessels by adjusting the size, number, and timing of action potentials. This message tells the blood vessels to constrict and the heart to beat faster, which increase blood pressure and ensures blood flow to vital organs. This dissertation provided new information regarding the action potential messages used by the sympathetic nervous system to communicate with the blood vessels and identified parts of our nervous system that are important for shaping these messages.
Klassen, Stephen A., "Action potential subpopulations in human muscle sympathetic nerve activity: discharge properties and governing mechanisms" (2019). Electronic Thesis and Dissertation Repository. 6624.
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Available for download on Friday, January 22, 2021