EVIDENCE FOR A STRYCHNINE-SENSITIVE MECHANISM AND GLYCINE RECEPTORS INVOLVED IN THE CONTROL OF URETHRAL SPHINCTER ACTIVITY DURING MICTURITION IN THE CAT

Micturition in the decerebrate cat is characterized by a coordinated b ladder contraction and a simultaneous decrease in external urethral sp hincter (EUS) efferent activity. Without the suppression of EUS activi ty, voiding is significantly impaired, resulting in a state sometimes referred to as bladder-sphincter dyssynergia. The aim of the present s tudy was to determine whether glycinergic inhibition contributes to th e suppression of EUS activity during micturition evoked by bladder dis tension or electrical stimulation of the pontine micturition center (P MC) in decerebrate cats. Using subconvulsive intravenous doses of stry chnine (0.1-0.24 mg/kg), we examined changes in bladder and EUS electr oneurographic (ENG) activity during micturition, Following subconvulsi ve doses of strychnine, tonic EUS ENG activity increased during bladde r filling in five of six animals. In the presence of strychnine, it wa s possible to evoke reflex bladder contractions of similar duration an d peak pressure to those observed before strychnine administration. Ho wever, there was an absence of suppression of EUS ENG activity during the bladder contractions in all the animals. To determine whether the changes in sphincter activity could be due to strychnine acting at gly cine receptors on EUS motoneurons, sacral spinal tissue was processed for a structural protein (gephyrin) associated with the glycine recept or. Motoneurons in Onuf's nucleus in S1 were identified using choline acetyltransferase immunohistochemistry and subsequently processed with a gephyrin monoclonal antibody. Abundant gephyrin labeling was eviden t throughout Onuf's nucleus. Since Onuf's nucleus is made up of EUS an d other motoneuron populations, a sample of antidromically identified urethral and anal sphincter motoneurons were intracellularly labeled w ith tetramethylrhodamine dextran (TMR-D) and then processed with the g ephyrin antibody. Using dual-beam confocal microscopy, gephyrin immuno reactivity was observed on the soma and proximal processes of individu al EUS motoneurons in both male and female animals. It was concluded t hat a strychnine-sensitive mechanism contributes to the suppression of sphincter activity normally observed during voiding. Although glycine rgic inhibition may affect several components of the circuitry respons ible for micturition, it appears that the suppression of EUS motoneuro ns during micturition may be partly due to a direct glycinergic inhibi tion of the EUS motoneurons.