title: Activation of neural circuitry and Ca2+ waves in longitudinal and circular muscle during CMMCs and the consequences of rectal aganglionosis in mice.
abstract: In mammals that develop rectal aganglionosis, the aganglionic segment still exhibits spontaneous phasic contractions that contribute to dysmotility and pseudoobstruction in this region. However, almost nothing is known about the mechanisms that generate these myogenic contractions or the effects of aganglionosis on the generation of Ca(2+) waves that underlie contractions of the longitudinal muscle (LM) and circular muscle (CM). In a mouse model of Hirschsprung's disease [endothelin type B receptor-deficient (Ednrb(s-l)/Ednrb(s-l)) mice], the Ca(2+) indicator fluo-4 was used to simultaneously monitor the temporal activation and spread of intercellular Ca(2+) waves in the LM and CM during spontaneous colonic motor activities. During the intervals between colonic migrating motor complexes (CMMCs) in control mice, Ca(2+) waves discharged asynchronously between the LM and CM. However, in these same mice, during CMMCs, a burst of discreet Ca(2+) waves fired simultaneously in both muscle layers, where the propagation velocity of Ca(2+) waves significantly increased, as did the rate of initiation and number of collisions between Ca(2+) waves. Hexamethonium (300 microM) or atropine (1 microM) prevented synchronized firing of Ca(2+) waves. In the aganglionic distal colon of Ednrb(s-l)/Ednrb(s-l) mice, not only were CMMCs absent, but Ca(2+) waves between the two muscle layers fired asynchronously, despite increased propagation velocity. The generation of CMMCs in control mice involves synchronized firing of enteric motor nerves to both the LM and CM, explaining the synchronized firing of discreet Ca(2+) waves between the two muscle layers. Aganglionosis results in a sporadic and sustained asynchrony in Ca(2+) wave firing between the LM and CM and an absence of CMMCs.
authors.affiliation: Dept of Physiology and Cell Biology, Univ of Nevada School of Medicine, Reno, NV 89557, USA. nick@unr.edu
authors.forename: Nick J
authors.initials: NJ
authors.lastname: Spencer
authors.forename: Peter
authors.initials: P
authors.lastname: Bayguinov
authors.forename: Grant W
authors.initials: GW
authors.lastname: Hennig
authors.forename: Kyu Joo
authors.initials: KJ
authors.lastname: Park
authors.forename: Hyun-Tai
authors.initials: HT
authors.lastname: Lee
authors.forename: Kenton M
authors.initials: KM
authors.lastname: Sanders
authors.forename: Terence K
authors.initials: TK
authors.lastname: Smith
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology*; D003106:Colon / Q000378:metabolism / Q000502:physiology* / Q000503:physiopathology; D004195:Disease Models, Animal; D005260:Female; D005769:Gastrointestinal Motility / Q000502:physiology; D006627:Hirschsprung Disease / Q000378:metabolism / Q000503:physiopathology*; D006984:Hypertrophy; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009130:Muscle, Smooth / Q000502:physiology* / Q000503:physiopathology; D016065:Myoelectric Complex, Migrating / Q000502:physiology*; D044023:Receptor, Endothelin B / Q000172:deficiency / Q000235:genetics / Q000502:physiology
chemical_list: D044023:Receptor, Endothelin B; D002118:Calcium