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Subregional Differences in GABAA Receptor Subunit Expression in the Rostral Ventrolateral Medulla of Sedentary Versus Physically Active Rats

Mueller, PJ;Fyk-Kolodziej, BE;Azar, TA;Llewellyn-Smith, IJ;

Neurons in the rostral ventrolateral medulla (RVLM) regulate blood pressure through direct projections to spinal sympathetic preganglionic neurons. Only some RVLM neurons are active under resting conditions due to significant, tonic inhibition by gamma-aminobutyric acid (GABA). Withdrawal of GABAA receptor-mediated inhibition of the RVLM increases sympathetic outflow and blood pressure substantially, providing a mechanism by which the RVLM could contribute chronically to cardiovascular disease (CVD). Here, we tested the hypothesis that sedentary conditions, a major risk factor for CVD, increase GABAA receptors in RVLM, including its rostral extension (RVLMRE ), both of which contain bulbospinal catecholamine (C1) and non-C1 neurons. We examined GABAA receptor subunits GABAA1 and GABAA2 in the RVLM/RVLMRE of sedentary or physically active (10-12weeks of wheel running) rats. Western blot analyses indicated that sedentary rats had lower expression of GABAA1 and GABAA2 subunits in RVLM but only GABAA2 was lower in the RVLMRE of sedentary rats. Sedentary rats had significantly reduced expression of the chloride transporter, KCC2, suggesting less effective GABA-mediated inhibition compared to active rats. Retrograde tracing plus triple-label immunofluorescence identified fewer bulbospinal non-C1 neurons immunoreactive for GABAA1 but a higher percentage of bulbospinal C1 neurons immunoreactive for GABAA1 in sedentary animals. Sedentary conditions did not significantly affect the number of bulbospinal C1 or non-C1 neurons immunoreactive for GABAA2 . These results suggest a complex interplay between GABAA receptor expression by spinally-projecting C1 and non-C1 neurons and sedentary versus physically active conditions. They also provide plausible mechanisms for both enhanced sympathoexcitatory and sympathoinhibitory responses following sedentary conditions. This article is protected by copyright. All rights reserved. 2019 Wiley Periodicals, Inc.