Year: 2019
Type: dissertation
Abstract: Tongue muscle tone, important for upper airway patency, is reduced during sleep due to the withdrawal of excitatory inputs to the hypoglossal motor nucleus (HMN). These wake-active neurotransmitters all inhibit TWIK-Related Acid-Sensitive Potassium (K+) leak (TASK-1/3) channels on hypoglossal motor neurons in vitro, increasing motor activity. We hypothesize that inhibition of hypoglossal TASK-1/3 channels will increase tongue muscle activity in-vivo, and modulate the responses to applied 5-HT, one such wake-active neurotransmitter. We microperfused the HMN of rats with several TASK-1/3 channel modulators and measured the resulting tongue muscle output, with or without co-applied 5-HT. Furthermore, the effects of 5-HT at the HMN were measured in mice lacking TASK-1/3 channels on hypoglossal motor neurons. This thesis identifies that TASK-1/3 channel modulation at the HMN does not modulate tongue muscle output or its response to 5-HT, suggesting that TASK-1/3 channels are not a suitable target for tongue muscle reactivation during sleep.
Source: TSpace (University of Toronto)
Author: Patrick Gurges
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W3147520172