title: Heterogeneities in ICC Ca2+ activity within canine large intestine.
abstract: OBJECTIVE
  In human and canine colon, both slow (slow waves, 2-8/min) and fast (myenteric potential oscillations [MPOs]; 16-20/min) electrical rhythms in the smooth muscle originate at the submucosal and myenteric borders, respectively. We used Ca(2+) imaging to investigate whether interstitial cells of Cajal (ICCs) at these borders generated distinct rhythms.
  
  
  METHODS
  Segments of canine colon were pinned with submucosal or myenteric surface uppermost or cut in cross section. Tissues were loaded with a Ca(2+) indicator (fluo-4), and activity was monitored at 36.5 +/- 0.5 degrees C using an electron multiplying charge coupled device (EMCCD).
  
  
  RESULTS
  Rhythmic, biphasic Ca(2+) transients (5-8/min), similar in waveform to electrical slow waves, propagated without decrement as a wave front (2-5 mm/s) through the ICC-SM network lying along the submucosal surface of the circular muscle (CM). In contrast, rhythmic intracellular Ca(2+) waves (approximately 16/min) and spontaneous reductions in Ca(2+) were observed in ICCs at the myenteric border (ICC-MY). Normally, intracellular Ca(2+) waves were unsynchronized between adjacent ICC-MY, although excitatory nerve activity synchronized activity. In addition, spontaneous reductions in Ca(2+) were observed that inhibited Ca(2+) waves. N omega-nitro-L-arginine (100 micromol/L; nitric oxide antagonist) blocked the reductions in Ca(2+) and increased the frequency (approximately 19/min) of intracellular Ca(2+) waves within ICC-MY.
  
  
  CONCLUSIONS
  ICC-SMs form a tightly coupled network that is able to generate and propagate slow waves. In contrast, Ca(2+) transients in ICC-MYs, which are normally not synchronized, have a similar duration and frequency as MPOs. Like MPOs, their activity is inhibited by nitrergic nerves and synchronized by excitatory nerves.
authors.affiliation: Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada, USA.
authors.forename: Hyun-Tai
authors.initials: HT
authors.lastname: Lee
authors.forename: Grant W
authors.initials: GW
authors.lastname: Hennig
authors.forename: Kyu Joo
authors.initials: KJ
authors.lastname: Park
authors.forename: Peter O
authors.initials: PO
authors.lastname: Bayguinov
authors.forename: Sean M
authors.initials: SM
authors.lastname: Ward
authors.forename: Kenton M
authors.initials: KM
authors.lastname: Sanders
authors.forename: Terence K
authors.initials: TK
authors.lastname: Smith
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D003106:Colon / Q000294:innervation* / Q000378:metabolism; D004285:Dogs; D004594:Electrophysiology; D017615:Enteric Nervous System / Q000502:physiology; D005260:Female; D005769:Gastrointestinal Motility / Q000502:physiology; D007413:Intestinal Mucosa / Q000294:innervation / Q000502:physiology; D008297:Male; D008564:Membrane Potentials; D008856:Microscopy, Fluorescence; D023421:Models, Animal; D009119:Muscle Contraction / Q000502:physiology*; D009197:Myenteric Plexus / Q000378:metabolism / Q000502:physiology*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism; D012680:Sensitivity and Specificity
chemical_list: D009569:Nitric Oxide; D002118:Calcium