GABAB-receptor-mediated suppression of sympathetic outflow from the spinal cord of neonatal rats

• Published in: Journal of applied physiology (1985) Vol. 99; no. 5; pp. 1658 - 1667
• Main Authors: Cheng, Yi-Wen, Ku, Min-Chi, Ho, Chiu-Ming, Chai, Chok-Yung, Su, Chun-Kuei
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Am Physiological Soc 01.11.2005; American Physiological Society
• Subjects: Age Factors; Animals; Animals, Newborn; Baclofen - analogs & derivatives; Baclofen - pharmacology; Biological and medical sciences; Cadmium - pharmacology; Calcium - metabolism; Cesium - pharmacology; Fundamental and applied biological sciences. Psychology; GABA Agonists - pharmacology; GABA Antagonists - pharmacology; Hypertension; Hypertension - physiopathology; Membrane Potentials - drug effects; Membrane Potentials - physiology; Nervous system; Neural Inhibition - drug effects; Neural Inhibition - physiology; Phosphinic Acids - pharmacology; Rats; Rats, Sprague-Dawley; Receptors, GABA-B - physiology; Respiratory system; Rodents; Spinal cord; Spinal Cord - growth & development; Spinal Cord - physiology; Splanchnic Nerves - growth & development; Splanchnic Nerves - physiology; Sympathetic Nervous System - growth & development; Sympathetic Nervous System - physiology; Hypertension; Spinal cord; Rat; Rodentia; Central nervous system; Cardiovascular disease; Sympathetic nervous system; Vertebrata; Mammalia; Postnatal; Autonomic nervous system; Intermediolateral nucleus; postnatal maturation; Gabaergic receptor B; intermediolateral cell column
• ISSN: 8750-7587; 1522-1601
• DOI: 10.1152/japplphysiol.00334.2005

1 Institute of Biomedical Sciences, Academia Sinica, and 2 Department 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 GABA B receptors in the regulation of SND. Despite an age-dependent difference in sensitivity, bath applications of baclofen (Bac; GABA B -receptor agonist) consistently reduced SND in a concentration-dependent manner. The drug specificity of Bac in activation of GABA B 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 Mg 2+ or 0.5 µM TTX to block Ca 2+ - 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 Cd 2+ -sensitive and high-voltage-activated inward currents, indicating an inhibition of voltage-gated Ca 2+ currents. Our results suggest that the activation of intraspinal GABA B receptors suppresses SND via a mixture of ion events that may link to a change in Ca 2+ 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 )