title: Bladder outlet obstruction causes up-regulation of nicotinic acetylcholine receptors in bladder-projecting pelvic ganglion neurons.
abstract: Pelvic ganglion (PG) neurons relay sympathetic and parasympathetic signals to the lower urinary tract, comprising the urinary bladder and bladder outlet, and are thus essential for both storage and voiding reflexes. Autonomic transmission is mediated by activation of the nicotinic acetylcholine receptor (nAChR) in PG neurons. Previously, bladder outlet obstruction (BOO), secondary to benign prostatic hyperplasia, was found to increase soma sizes of bladder-projecting PG neurons. To date, however, it remains unknown whether these morphological changes are accompanied by functional plasticity in PG neurons. In the present study, we investigated whether BOO alters acetylcholine receptor (nAChR) transcript expression and current density in bladder PG neurons. Partial ligation of the rat urethra for six weeks induced detrusor overactivity (DO), as observed during cystometrical measurement. In rats exhibiting DO, membrane capacitance of parasympathetic bladder PG neurons was selectively increased. Real-time PCR analysis revealed that BOO enhanced the expression of the transcripts encoding the nAChR α3 and β4 subunits in PG neurons. Notably, BOO significantly increased ACh-evoked current density in parasympathetic bladder PG neurons, whereas no changes were observed in sympathetic bladder and parasympathetic penile PG neurons. In addition, other ligand-gated ionic currents were immune to BOO in bladder PG neurons. Taken together, these data suggest that BOO causes upregulation of nAChR in parasympathetic bladder PG neurons, which in turn may potentiate ganglionic transmission and contribute to the development of DO.
authors.affiliation: Department of Urology, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea. Electronic address: chc7174@yonsei.ac.kr.
authors.forename: Hyun-Chul
authors.initials: HC
authors.lastname: Chung
authors.affiliation: Department of Physiology, Brain Research Group, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea. Electronic address: soe279@naver.com.
authors.forename: Choong-Ku
authors.initials: CK
authors.lastname: Lee
authors.affiliation: Department of Pathology, Brain Research Group, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea. Electronic address: abba@yonsei.ac.kr.
authors.forename: Kwang-Hwa
authors.initials: KH
authors.lastname: Park
authors.affiliation: Department of Physiology, Brain Research Group, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea. Electronic address: swjeong@yonsei.ac.kr.
authors.forename: Seong-Woo
authors.initials: SW
authors.lastname: Jeong
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000502:physiology; D004195:Disease Models, Animal; D025802:Electric Capacitance; D008297:Male; D056347:Neuroanatomical Tract-Tracing Techniques; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D017777:Parasympathetic Fibers, Postganglionic / Q000378:metabolism / Q000473:pathology; D018408:Patch-Clamp Techniques; D010413:Penis / Q000294:innervation; D011877:Radionuclide Imaging; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D011978:Receptors, Nicotinic / Q000378:metabolism*; D017779:Sympathetic Fibers, Postganglionic / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation; D001743:Urinary Bladder / Q000000981:diagnostic imaging* / Q000473:pathology; D001748:Urinary Bladder Neck Obstruction / Q000378:metabolism* / Q000473:pathology; D053201:Urinary Bladder, Overactive / Q000378:metabolism* / Q000473:pathology
chemical_list: D011978:Receptors, Nicotinic
keywords: Bladder outlet obstruction; Detrusor overactivity; Ganglionic transmission; Nicotinic acetylcholine receptor; Parasympathetic; Pelvic ganglion