title: Down-regulation of L-type calcium channels in inflamed circular smooth muscle cells of the canine colon.
abstract: OBJECTIVE
  Circular smooth muscle phasic contractions and tone are suppressed during colonic inflammation, but the contributing factors are poorly understood. This study investigated if the expression level of voltage-gated long-lasting (L-type) Ca(2+) channel protein and functional Ca(2+) channel current are down-regulated in the circular muscle cells of the inflamed canine colon.
  
  
  METHODS
  L-type Ca(2+) channel expression was compared between normal and inflamed smooth muscle cells by Western immunoblots using an antibody directed against the pore-forming alpha 1C-subunit, and patch-clamp methods were used to evaluate Ca(2+) channel current density.
  
  
  RESULTS
  The expression of the L-type Ca(2+) channel protein was significantly reduced in inflamed compared with normal circular smooth muscle cell membranes, and this finding was associated with suppressed levels of Ca(2+) channel current in patch-clamped cells. The L-type Ca(2+) channel current in normal and inflamed cells increased proportionately in response to Bay K 8644, but the maximal current density was still lower in the inflamed cells. Acetylcholine increased the L-type Ca(2+) channel current in normal but not in inflamed cells.
  
  
  CONCLUSIONS
  The expression level of L-type Ca(2+) channels is down-regulated in the circular smooth muscle cell membranes of the inflamed colon, which may result in reduced Ca(2+) influx. The functional and pharmacologic properties of the channels seem normal. Although some Ca(2+) channels are still present in the inflamed cells, acetylcholine does not activate these channels, which may be caused by additional upstream defects in the receptor signaling cascade. The down-regulation of L-type Ca(2+) channel expression may suppress circular smooth muscle contractions in the inflamed colon and contribute to the abnormalities in motility and digestion observed during inflammatory disorders.
authors.affiliation: Department of Surgery, Medical College of Wisconsin and Zablocki VA Medical Center, Milwaukee, Wisconsin, USA.
authors.forename: X
authors.initials: X
authors.lastname: Liu
authors.forename: N J
authors.initials: NJ
authors.lastname: Rusch
authors.forename: J
authors.initials: J
authors.lastname: Striessnig
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; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000032:analysis / Q000378:metabolism*; D003092:Colitis / Q000276:immunology / Q000378:metabolism*; D003106:Colon / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D004285:Dogs; D015536:Down-Regulation / Q000502:physiology; D005260:Female; D015151:Immunoblotting; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000032:analysis / Q000378:metabolism
chemical_list: D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D015221:Potassium Channels; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009543:Nifedipine; D000109:Acetylcholine; D002118:Calcium