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Publication : The role of GαO-mediated signaling in the rostral ventrolateral medulla oblongata in cardiovascular reflexes and control of cardiac ventricular excitability.

First Author  Ang R Year  2016
Journal  Physiol Rep Volume  4
Issue  15 PubMed ID  27528004
Mgi Jnum  J:294336 Mgi Id  MGI:6455251
Doi  10.14814/phy2.12860 Citation  Ang R, et al. (2016) The role of GalphaO-mediated signaling in the rostral ventrolateral medulla oblongata in cardiovascular reflexes and control of cardiac ventricular excitability. Physiol Rep 4(15)
abstractText  The heart is controlled by the sympathetic and parasympathetic limbs of the autonomic nervous system with inhibitory signaling mechanisms recruited in both limbs. The aim of this study was to determine the role of inhibitory heterotrimeric G proteins in the central nervous mechanisms underlying autonomic control of the heart and its potential role in arrhythmogenesis. Mice with conditional deletion of the inhibitory heterotrimeric G protein GalphaO in the presympathetic area of the rostral ventral lateral medulla (RVLM) were generated to determine the role of GalphaO-mediated signalling in autonomic control and electrophysiological properties of the heart. GalphaO deletion within the RVLM was not associated with changes in heart rate (HR) or the arterial blood pressure at rest (home cage, normal behavior). However, exposure to stressful conditions (novel environment, hypoxia, or hypercapnia) in these mice was associated with abnormal HR responses and an increased baroreflex gain when assessed under urethane anesthesia. This was associated with shortening of the ventricular effective refractory period. This phenotype was reversed by systemic beta-adrenoceptor blockade, suggesting that GalphaO depletion in the RVLM increases central sympathetic drive. The data obtained support the hypothesis that GalphaO-mediated signaling within the presympathetic circuits of the RVLM contributes to the autonomic control of the heart. GalphaO deficiency in the RVLM has a significant impact on cardiovascular responses to stress, cardiovascular reflexes and electrical properties of the heart.
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