Regulation of GABAA Receptor by Protein Kinase A in Sympathetic Neurons of Major Pelvic Ganglia

Abstract

Major pelvic ganglia (MPG) in rats are an unique autonomic ganglia, containing both sympathetic and parasympathetic neurons related with the function of bladder, penis and bowel. It has been widely known that ionotropic GABAA receptors are the molecular target of γ-aminobutyric acid (GABA), a major inhibitory neurotransmitter in central nervous system. However, their functions and regulations of GABAA receptors expressed in autonomic ganglia have been poorly understood. I examined the modulatory role of adenylyl cyclase (AC) and protein kinase A (PKA) on GABAA-induced inward currents in the neurons of rat MPG. GABAA receptors were identified using immunofluorescent labeling in the rat major pelvic ganglion. Electrophysiological experiments were performed to record the activities of GABAA receptors. GABAA receptors were expressed only in sympathetic neurons. GABA induced marked inward currents in a concentration-dependent manner. Mucimol (5 μM), a GABAA receptor agonist, induced inward currents were significantly reduced in the presence of SQ 225361 20 μM, a AC inhibitor and myristoylated PKA inhibitor 100 nM. In addition, forskolin (1 μM), AC activator, augmented the GABA induced currents. The activation of AC/PKA-dependent pathway could involve in the regulation GABAA receptors, expressed only in sympathetic neurons of rat MPG. These findings are helpful for the better understanding the function of various pelvic organs innervated by MPG.