title: Impairment of Ca(2+) mobilization in circular muscle cells of the inflamed colon.
abstract: This study investigated whether inflammation modulates the mobilization of Ca(2+) in canine colonic circular muscle cells. The contractile response of single cells from the inflamed colon was significantly suppressed in response to ACh, KCl, and BAY K8644. Methoxyverapamil and reduction in extracellular Ca(2+) concentration dose-dependently blocked the response in both normal and inflamed cells. The increase in intracellular Ca(2+) concentration in response to ACh and KCl was significantly reduced in the inflamed cells. However, Ca(2+) efflux from the ryanodine- and inositol 1,4, 5-trisphosphate (IP(3))-sensitive stores, as well as the decrease of cell length in response to ryanodine and IP(3), were not affected. Heparin significantly blocked Ca(2+) efflux and contraction in response to ACh in both conditions. ACh-stimulated accumulation of IP(3) and the binding of [(3)H]ryanodine to its receptors were not altered by inflammation. Ruthenium red partially inhibited the response to ACh in normal and inflamed states. We conclude that the canine colonic circular muscle cells utilize Ca(2+) influx through L-type channels as well as Ca(2+) release from the ryanodine- and IP(3)-sensitive stores to contract. Inflammation impairs Ca(2+) influx through L-type channels, but it may not affect intracellular Ca(2+) release. The impairment of Ca(2+) influx may contribute to the suppression of circular muscle contractility in the inflamed state.
authors.affiliation: Departments of Surgery and Physiology, Medical College of Wisconsin and Zablocki Veterans Affairs Medical Center, Milwaukee, Wisconsin 53226, USA.
authors.forename: X Z
authors.initials: XZ
authors.lastname: Shi
authors.forename: S K
authors.initials: SK
authors.lastname: Sarna
mesh_terms: D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002132:Calcium Radioisotopes; D002463:Cell Membrane Permeability; D048429:Cell Size / Q000187:drug effects; D003092:Colitis / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D004285:Dogs; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism / Q000494:pharmacology; D007700:Kinetics; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000166:cytology / Q000378:metabolism*; D011189:Potassium Chloride / Q000494:pharmacology; D012433:Ryanodine / Q000378:metabolism / Q000494:pharmacology; D014316:Tritium
chemical_list: D002120:Calcium Channel Agonists; D002132:Calcium Radioisotopes; D014316:Tritium; D012433:Ryanodine; D011189:Potassium Chloride; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D015544:Inositol 1,4,5-Trisphosphate; D000109:Acetylcholine; D002118:Calcium