MP30-12 SPONTANEOUS ACTIVITY OF THE HUMAN DETRUSOR DEPENDS ON THE RATIO BETWEEN CONTRACTILE RESPONSES TO NERVE STIMULATION AND ANTICHOLINERGIC EFFECTS OF PROTEIN KINASE C ACTIVATION

Abstract

You have accessJournal of UrologyBladder & Urethra: Anatomy, Physiology & Pharmacology II1 Apr 2016MP30-12 SPONTANEOUS ACTIVITY OF THE HUMAN DETRUSOR DEPENDS ON THE RATIO BETWEEN CONTRACTILE RESPONSES TO NERVE STIMULATION AND ANTICHOLINERGIC EFFECTS OF PROTEIN KINASE C ACTIVATION Joseph Hypolite, Randall Meecham, and Anna Malykhina Joseph HypoliteJoseph Hypolite More articles by this author , Randall MeechamRandall Meecham More articles by this author , and Anna MalykhinaAnna Malykhina More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.1244AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Urinary bladder function includes the ability to store urine at low intravesical pressure followed by a subsequent voiding due to a rapid phasic contraction. Neurotransmitters released by electrical field stimulation (EFS) have been shown to modulate human detrusor smooth muscle (HDSM) contractility via protein kinase C (PKC)-dependent pathways, while potassium chloride (KCl) depolarization increases contractility via activation of voltage gated calcium channels. The objective of this study was to identify the factors predictive of spontaneous activity in HDSM under physiological conditions. METHODS Experiments were conducted in vitro using detrusor smooth muscle strips isolated from full thickness human bladder specimens (N=7, 35±5.5 yr). Contractile responses to EFS (80 volts, 32 Hz, 1ms duration), KCl (125 mM), carbachol (0.1-100 µM), and phorbol,12-13 dibutyrate (PDBu) 1µM, a PKC activator, were tested in organ bath studies. All contractions were normalized to the maximal KCl response taken as 100% (n=42). Data was analyzed by ANOVA with p=0.05 being statistically significant. RESULTS The maximal amplitude (peak force) of contractile responses of HDSM strips to EFS and carbachol was approximately 2-fold higher in comparison to KCl stimulation (232±15% and 236±17%, respectively, p=0.05 to KCl stimulation). Muscle strips in which the EFS/KCL force ratio was greater than 100% (119%±14.1, high-ratio group) did not show spontaneous contractions, whereas the strips with EFS/KCl ratio of 68±6.5% (low ratio group) revealed consistent spontaneous activity. Upon stimulation with carbachol, EC50 for high-ratio group was 0.35±0.021 µM, and 1.2±0.09 µM for the low EFS/KCl ratio, respectively (p=0.05). A significant contractile response of HDSM to PDBu was associated with increased tone in response to muscarinic stimulation but low incidence of spontaneous contractions. CONCLUSIONS The results of our study provide evidence that the ratio between the peak contractile responses of HDSM contractions to EFS versus KCl is predictive of spontaneous contractile activity present in the bladder wall. When EFS/KCl ratio is higher than 100%, the detrusor tends to be more quiet with no spontaneous contractions but higher sensitivity to muscarinic receptor stimulation. When the EFS/KCl ratio is lower than 100%, the detrusor shows more spontaneous activity and lower response to muscarinic activation. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e415-e416 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Joseph Hypolite More articles by this author Randall Meecham More articles by this author Anna Malykhina More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...