Subregional differences in GABA_A receptor subunit expression in the rostral ventrolateral medulla of sedentary versus...

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 GABA_A 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 GABA_A receptors in RVLM, including its rostral extension (RVLM_RE ), both of which contain bulbospinal catecholamine (C1) and non-C1 neurons. We examined GABA_A receptor subunits GABA_Aα1 and GABA_Aα2 in the RVLM/RVLM_RE of sedentary or physically active (10-12 weeks of wheel running) rats. Western blot analyses indicated that sedentary rats had lower expression of GABA_Aα1 and GABA_Aα2 subunits in RVLM but only GABA_Aα2 was lower in the RVLM_RE 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 GABA_Aα1 but a higher percentage of bulbospinal C1 neurons immunoreactive for GABA_Aα1 in sedentary animals. Sedentary conditions did not significantly affect the number of bulbospinal C1 or non-C1 neurons immunoreactive for GABA_Aα2 . These results suggest a complex interplay between GABA_A 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.