Modulation of GABAA Receptor by Protein Kinase C in Autonomic Major Pelvic Ganglion Neurons

Abstract

γ-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the central nervous system, and its actions are mediated by subtypes of GABA receptors named as GABAA, GABAB, and GABAC. GABAA, receptor consisting of α, β, γ and δ subunits is a heterooligomeric ligand-gated chloride channel. This study was performed to investigate regulation of GABAA receptor by protein kinase C (PKC). Ion currents were recorded using gramicidine-perforated patch and whole cell patch clamp. mRNA encoding the subunits of PKC expressed in major pelvic ganglion (MPG) neurons was detected by using RT-PCR. The GABA-induced inward current was increased by PKC activators and decreased by PKC inhibitors, respectively. These effects were not associated with intracellular Ca2+ and OAG (1-oleoyl-2-acetyl-sn-glycerol), a membrane permeable diacylglycerol (DAG) analogue. These results mean that the subfamily of PKC participating in activation of GABAA receptor would be an atypical PKC (aPKC). Among theses, ξ isoform of aPKC was detected by RT-PCR. Taking together, we suggest that excitable GABAA receptor in sympathetic MPG neuron seemed to be regulated by aPKC, particular in ξ isoform. The regulatory roles of PKC on excitatory GABAA receptors in sympathetic neurons of MPG may be an important factor to control the functional activity of various pelvic organs such as bowel movement, micturition and erection.