title: Origin of spontaneous activity in neonatal and adult rat bladders and its enhancement by stretch and muscarinic agonists.
abstract: This study examined the origin of spontaneous activity in neonatal and adult rat bladders and the effect of stretch and muscarinic agonists and antagonists on spontaneous activity. Rats were anesthetized and their bladders were excised, cannulated, and loaded with voltage- and Ca(2+)-sensitive dyes. Intracellular Ca(2+) and membrane potential transients were mapped using photodiode arrays in whole bladders, bladder sheets, or cross-section preparations at 37 degrees C. Intravesical pressure was recorded from whole bladders. In neonatal bladders and sheets, spontaneous Ca(2+) and electrical signals arose at a site near the dome and spread in a coordinated manner throughout the bladder with different dome-to-neck conduction velocities (Ca(2+): 3.7 +/- 0.4 mm/s; membrane potential: 46.2 +/- 3.1 mm/s). In whole bladders, optical signals were associated with spontaneous contractions (10-20 cmH(2)O). By contrast, in adult bladders spontaneous Ca(2+) and electrical activity was uncoordinated, originating at multiple sites and was associated with smaller (2-5 cmH(2)O) contractions. Spontaneous contractions and optical signals were insensitive to tetrodotoxin (2 muM) but were blocked by nifedipine (10 muM). Stretch or low carbachol concentrations (50 nM) applied to neonatal whole bladders enhanced the amplitude (to 20-35 cmH(2)O) of spontaneous activity, which was blocked by atropine. Bladder cross sections revealed that Ca(2+) and membrane potential transients produced by stretch or carbachol began near the urothelial-suburothelial interface and then spread to the detrusor. In conclusion, spontaneous activity in neonatal bladders, unlike activity in adult bladders, is highly organized, originating in the urothelium-suburothelium near the dome. Activity is enhanced by stretch or carbachol and this enhancement is blocked by atropine. It is hypothesized that acetylcholine is released from the urothelium during bladder filling to enhance spontaneous activity.
authors.affiliation: Department of Medicine, University of Pittsburgh School of Medicine, A1224 Scaife Hall, Pittsburgh, PA 15261, USA. ajk5@pitt.edu
authors.forename: A
authors.initials: A
authors.lastname: Kanai
authors.forename: J
authors.initials: J
authors.lastname: Roppolo
authors.forename: Y
authors.initials: Y
authors.lastname: Ikeda
authors.forename: I
authors.initials: I
authors.lastname: Zabbarova
authors.forename: C
authors.initials: C
authors.lastname: Tai
authors.forename: L
authors.initials: L
authors.lastname: Birder
authors.forename: D
authors.initials: D
authors.lastname: Griffiths
authors.forename: W
authors.initials: W
authors.lastname: de Groat
authors.forename: C
authors.initials: C
authors.lastname: Fry
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001285:Atropine / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects; D002217:Carbachol / Q000494:pharmacology; D003931:Diacetyl / Q000031:analogs & derivatives / Q000494:pharmacology; D004558:Electric Stimulation; D004594:Electrophysiology; D006874:Hydrostatic Pressure; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D018721:Muscarinic Agonists / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D010812:Physical Stimulation; D051381:Rats; D013498:Suramin / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D001743:Urinary Bladder / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D019459:Urothelium / Q000187:drug effects / Q000502:physiology
chemical_list: D018721:Muscarinic Agonists; C004717:diacetylmonoxime; D013779:Tetrodotoxin; D013498:Suramin; D001285:Atropine; D002217:Carbachol; D003931:Diacetyl