Activating the cAMP-PKA pathway modulates genioglossus muscle and responses to excitatory inputs.
Published: 2005
Language: eng
Number of pages: 118
Description: Whether modulation of intracellular pathways increases pharyngeal muscle activity has not been investigated but is relevant to treat obstructive sleep apnea. This study determines whether modulating cyclic-adenosine-3'-5'-monophosphate (cAMP) at the hypoglossal motor nucleus (HMN) increases genioglossus (GG) muscle activity across sleep-wake states. Electrodes were implanted to record sleep-wake states and respiratory muscle activity. Microdialysis probes were inserted into the HMN to perfuse artificial-cerebrospinal-fluid (ACSF) alone or with forskolin (adenylyl cyclase activator to increase cAMP), a cAMP analogue, or iso-butyl-methylxanthine (IBMX, phosphodiesterase inhibitor to prevent breakdown of CAMP). Compared to ACSF, forskolin and the CAMP analogue increased GG activity during wakefulness and non-REM sleep but not REM sleep. IBMX did not affect GG activity but selectively abolished responses to serotonin and phenylephrine and preserved responses to (S)-2-amino-3-(3-hydroxy-5-phenyl-4-isoxazolyl)-propionic acid, AMPA. These effects were mimicked by a cGMP analogue. In conclusion, modulating the cAMP pathway altered GG activity and responses to excitatory inputs.
Notes: Source: Masters Abstracts International, Volume: 44-02, page: 0768.

Thesis (M.Sc.)--University of Toronto, 2005.

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