GABAB Mediated Regulation of Sympathetic Preganglionic Neurons: Pre- and Postsynaptic Sites of Action

Abstract

Modulatory influences on sympathetic nervous system activity are diverse and far reaching, acting at select points in the complex pathways controlling sympathetic outflow to enable subtle changes or more global effects. Changes in the degree of sympathetic neuromodulation can have serious consequences on homeostatic variables such as heart rate, blood pressure and gut motility. At the level of the spinal cord, the sympathetic preganglionic neurons (SPNs) can be modulated by activation of presynaptic GABAB heteroreceptors on glutamatergic terminals and by postsynaptic GABAB receptors. Here we show that a low concentration of the GABAB agonist baclofen (1 μM) attenuated GABAergic inhibitory postsynaptic potentials in SPNs elicited from stimulation of either the central autonomic area or descending fibers in the lateral funiculus. This low baclofen concentration also elicited three categories of postsynaptic response: a large hyperpolarization with a decrease in input resistance, a moderate hyperpolarization with no change in input resistance and no response. Using cesium-loaded, tetraethylammonium chloride containing electrodes (to block potassium conductance), baclofen elicited moderate hyperpolarizations with no change in input resistance in 50% of SPNs; the remainder were unaffected. These modest hyperpolarizations were reduced in Ca2+ free solution or cadmium. Hyperpolarizing responses were also observed in interneurons in the vicinity of SPNs. These studies provide the first evidence for GABAB autoreceptors involved in inhibitory GABAergic transmission onto SPNs and for postsynaptic GABAB receptors on interneurons. The data also indicate that there is heterogeneity in the postsynaptic responses of SPNs.

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