title: Basal cGMP regulates the resting pacemaker potential frequency of cultured mouse colonic interstitial cells of Cajal.
abstract: Cyclic guanosine 3',5'-monophosphate (cGMP) inhibited the generation of pacemaker activity in interstitial cells of Cajal (ICCs) from the small intestine. However, cGMP role on pacemaker activity in colonic ICCs has not been reported yet. Thus, we investigated the role of cGMP in pacemaker activity regulation by colonic ICCs. We performed a whole-cell patch-clamp and Ca(2+) imaging in cultured ICCs from mouse colon. 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, an inhibitor of guanylate cyclase) increased the pacemaker potential frequency, whereas zaprinast (an inhibitor of phosphodiesterase) and cell-permeable 8-bromo-cGMP decreased the pacemaker potential frequency. KT-5823 (an inhibitor of protein kinase G [PKG]) did not affect the pacemaker potential. L-N(G)-nitroarginine methyl ester (L-NAME, an inhibitor of nitric oxide [NO] synthase) increased the pacemaker potential frequency, whereas (±)-S-nitroso-N-acetylpenicillamine (SNAP, a NO donor) decreased the pacemaker potential frequency. Glibenclamide (an ATP-sensitive K(+) channel blocker) did not block the effects of cell-permeable 8-bromo-cGMP and SNAP. Recordings of spontaneous intracellular Ca(2+) ([Ca(2+)]i) oscillations revealed that ODQ and L-NAME increased [Ca(2+)]i oscillations. In contrast, zaprinast, 8-bromo cGMP, and SNAP decreased the [Ca(2+)]i oscillations. Basal cGMP levels regulate the resting pacemaker potential frequency by the alteration on Ca(2+) release via a PKG-independent pathway. Additionally, the endogenous release of NO seems to be responsible maintaining basal cGMP levels in colonic ICCs.
authors.affiliation: Department of Physiology, College of Medicine, Chosun University, 309 Pilmun-daero, Dongku, Gwangju, 501-375, Korea.
authors.forename: Pawan Kumar
authors.initials: PK
authors.lastname: Shahi
authors.forename: Seok
authors.initials: S
authors.lastname: Choi
authors.forename: Yu Jin
authors.initials: YJ
authors.lastname: Jeong
authors.forename: Chan Guk
authors.initials: CG
authors.lastname: Park
authors.forename: Insuk
authors.initials: I
authors.lastname: So
authors.forename: Jae Yeoul
authors.initials: JY
authors.lastname: Jun
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D003106:Colon / Q000166:cytology*; D006152:Cyclic GMP / Q000502:physiology*; D005260:Female; D056885:Interstitial Cells of Cajal / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000378:metabolism
chemical_list: D009569:Nitric Oxide; D006152:Cyclic GMP; D002118:Calcium