Changes in guinea pig gallbladder smooth muscle Ca2+ homeostasis by acute acalculous cholecystitis.
Impaired smooth muscle contractility is a hallmark of acute acalculous cholecystitis. Although free cytosolic Ca2+ ([Ca2+]i) is a critical step in smooth muscle contraction, possible alterations in Ca2+ homeostasis by cholecystitis have not been elucidated. Our aim was to elucidate changes in the Ca2+ signaling pathways induced by this gallbladder dysfunction. [Ca2+]i was determined by epifluorescence microscopy in fura 2-loaded isolated gallbladder smooth muscle cells, and isometric tension was recorded from gallbladder muscle strips. F-actin content was quantified by confocal microscopy. Ca2+ responses to the inositol trisphosphate (InsP3) mobilizing agonist CCK and to caffeine, an activator of the ryanodine receptors, were impaired in cholecystitic cells. This impairment was not the result of a decrease in the size of the releasable pool. Inflammation also inhibited Ca2+ influx through L-type Ca2+ channels and capacitative Ca2+ entry induced by depletion of intracellular Ca2+ pools. In addition, the pharmacological phenotype of these channels was altered in cholecystitic cells. Inflammation impaired contractility further than Ca2+ signal attenuation, which could be related to the decrease in F-actin that was detected in cholecystitic smooth muscle cells. These findings indicate that cholecystitis decreases both Ca2+ release and Ca2+ influx in gallbladder smooth muscle, but a loss in the sensitivity of the contractile machinery to Ca2+ may also be responsible for the impairment in gallbladder contractility.
Gomez-Pinilla
Pedro J
PJ
Department of Physiology, Nursing School, University of Extremadura, Cáceres, Spain.
Morales
Sara
S
Camello-Almaraz
Cristina
C
Moreno
Rosario
R
Pozo
María J
MJ
Camello
Pedro J
PJ
D042101:Acalculous Cholecystitis / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D005704:Gallbladder / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D006168:Guinea Pigs; D006706:Homeostasis; D008297:Male; D009119:Muscle Contraction / Q000502:physiology; D009130:Muscle, Smooth / Q000378:metabolism*; D009568:Nitrendipine / Q000494:pharmacology; D015398:Signal Transduction; D019284:Thapsigargin / Q000494:pharmacology
D019284:Thapsigargin; D009568:Nitrendipine; D002118:Calcium