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J Appl Physiol 99: 1658-1667, 2005. First published July 21, 2005; doi:10.1152/japplphysiol.00334.2005
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GABAB-receptor-mediated suppression of sympathetic outflow from the spinal cord of neonatal rats

Yi-Wen Cheng,1 Min-Chi Ku,1 Chiu-Ming Ho,2 Chok-Yung Chai,1 and Chun-Kuei Su1

1Institute of Biomedical Sciences, Academia Sinica, and 2Department of Anesthesiology, Taipei Veterans General Hospital and National Yang-Ming University, Taipei, Taiwan

Submitted 23 March 2005 ; accepted in final form 14 July 2005

Using a splanchnic nerve-spinal cord preparation in vitro that could spontaneously generate sympathetic nerve discharge (SND), we investigated the roles of intraspinal GABAB receptors in the regulation of SND. Despite an age-dependent difference in sensitivity, bath applications of baclofen (Bac; GABAB-receptor agonist) consistently reduced SND in a concentration-dependent manner. The drug specificity of Bac in activation of GABAB receptors was verified by application of its antagonist saclofen (Sac) or CGP-46381 (CGP). Sac or CGP alone did not change SND. However, in the presence of Sac or CGP, the effects of Bac on SND inhibition were reversibly attenuated. The splanchnic sympathetic preganglionic neuron (SPN) was recorded by blind whole cell, patch-clamp techniques. We examined Bac effects on electrical membrane properties of SPNs. Applications of Bac reduced excitatory synaptic events, induced membrane hyperpolarizations, and inhibited SPN firing. In the presence of 12 mM Mg2+ or 0.5 µM TTX to block Ca2+- or action potential-dependent synaptic transmissions, applications of Bac induced an outward baseline current that reversed at –29 ± 6 mV. Because the K+ equilibrium potential in our experimental conditions was –100 mV, the Bac-induced currents could not simply be attributed to an alteration of K+ conductance. On the other hand, applications of Bac to Cs+-loaded SPNs reduced Cd2+-sensitive and high-voltage-activated inward currents, indicating an inhibition of voltage-gated Ca2+ currents. Our results suggest that the activation of intraspinal GABAB receptors suppresses SND via a mixture of ion events that may link to a change in Ca2+ conductance.

intermediolateral cell column; hypertension; postnatal maturation; autonomic nervous system



Address for reprint requests and other correspondence: C.-K. Su, Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan (e-mail: csu{at}ibms.sinica.edu.tw)




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FASEB J.Home page
L. Wang, J. Deuchars, and S. A Deuchars
GABAB receptors decrease inhibitory synaptic transmission onto sympathetic preganglionic neurones (SPNs) in the rat spinal cord slice preparation.
FASEB J, April 1, 2007; 21(6): A884 - A884.



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Anesth. Analg.Home page
C.-M. Ho and C.-K. Su
Ketamine Attenuates Sympathetic Activity Through Mechanisms not Mediated by N-Methyl-d-Aspartate Receptors in the Isolated Spinal Cord of Neonatal Rats.
Anesth. Analg., March 1, 2006; 102(3): 806 - 810.
[Abstract] [Full Text] [PDF]




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