title: Pacemaking activity is regulated by membrane stretch via the CICR pathway in cultured interstitial cells of Cajal from murine intestine.
abstract: Membrane stretch is an important stimulus in gastrointestinal (GI) motility regulation, but the relationship between membrane stretch and the pacemaking activity of GI smooth muscle is poorly understood. We examined the effect of intestinal distension on slow waves and the effect of membrane stretch on pacemaker currents in cultured intestinal interstitial cells of Cajal (ICCs) from murine small intestine. At organ level, intestinal distension significantly increased amplitude of slow and fast waves, and enhanced frequencies of fast but not slow waves. At the cellular level, membrane stretch-induced by hyposmotic cell swelling (MSHC) depolarized membrane potential and activated large inward holding current, but suppressed amplitude of pacemaker potential or pacemaking current. External Ca(2+)-free solution abolished pacemaker current and blocked MSHC-induced inward holding current. However, a sustained inward holding current was activated and the amplitude of pacemaker current was increased by high ethylene glycol tetraacetic acid (EGTA) in pipette. Then MSHC also potentiated the inward holding current. MSHC significantly increased amplitude of rhythmic Ca(2+) transients and basal intracellular Ca(2+) concentration ([Ca(2+)](i)). 2-APB blocked both pacemaker current and Ca(2+) transients but did not alter the effect of MSHC on pacemaker current and Ca(2+) transients. In contrast, ryanodine inhibited Ca(2+) transients but not pacemaker current, and completely blocked MSHC-induced inward holding current and MSHC-induced increase of basal [Ca(2+)](i). These results suggest that intestinal distension potentiates intestinal motility by increasing the amplitude of slow waves. Membrane stretch potentiates pacemaking activity via releasing Ca(2+) from calcium-induced calcium release (CICR) in cultured intestinal ICCs.
authors.affiliation: Department of Physiology, Shanghai Jiaotong University School of Medicine, Shanghai 200240, China.
authors.forename: Zuo Yu
authors.initials: ZY
authors.lastname: Wang
authors.forename: Yan Fei
authors.initials: YF
authors.lastname: Han
authors.forename: Xu
authors.initials: X
authors.lastname: Huang
authors.forename: Peng
authors.initials: P
authors.lastname: Zhao
authors.forename: Hong Li
authors.initials: HL
authors.lastname: Lu
authors.forename: Young Chul
authors.initials: YC
authors.lastname: Kim
authors.forename: Wen Xie
authors.initials: WX
authors.lastname: Xu
mesh_terms: D000818:Animals; D001683:Biological Clocks / Q000502:physiology*; D020013:Calcium Signaling / Q000502:physiology*; D002462:Cell Membrane / Q000502:physiology*; D002478:Cells, Cultured; D055119:Elastic Modulus; D025461:Feedback, Physiological / Q000502:physiology; D005769:Gastrointestinal Motility / Q000502:physiology*; D056885:Interstitial Cells of Cajal / Q000502:physiology*; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C