IFLYSIB 05383
INSTITUTO DE FISICA DE LIQUIDOS Y SISTEMAS BIOLOGICOS
Unidad Ejecutora - UE
artículos
Título:
Negative feedback of extracellular ADP on ATP release in goldfish hepatocytes: A theoretical study
Autor/es:
CHARA OSVALDO; PAFUNDO DIEGO; SCHWARZBAUM PABLO JULIO
Revista:
JOURNAL OF THEORETICAL BIOLOGY
Editorial:
ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD
Referencias:
Lugar: Amsterdam, Netherlands; Año: 2010 vol. 264 p. 1147 - 1158
ISSN:
0022-5193
Resumen:
A mathematicalmodelwasbuilttoaccountforthekineticofextracellularATP(ATPe)andextracellularADP (ADPe)concentrationsfromgoldfishhepatocytesexposedtohypotonicity.ThemodelwasbasedonpreviousexperimentalresultsonthetimecourseofATPeaccumulation,ectoATPaseactivity,andcellviability[Pafundo etal.,2008].The kineticofATPeiscontrolledbyalyticATPflux,anon-lyticATPflux,andecto-ATPaseactivity,whereasADPekineticisgovernedbyalyticADPfluxandbothecto-ATPaseandecto-ADPaseactivities.Non-lyticATPeeffluxwasincludedasadiffusionequationmodulatedbyATPeactivation(positivefeedback)andADPeinhibition(negativefeedback).The modelyieldedphysicallymeaningfulandstablesteady-statesolutions,wasabletofittheexperimentaltimeevolutionofATPeandsimulatedtheconcomitantkineticofADPe.AccordingtothemodelduringthefirstminuteofhypotonicitytheconcentrationofATPeismainlygovernedbybothlytic andnon-lyticATPefflux,withalmostnocontributionfromecto-ATPaseactivity.Lateron,ecto-ATPaseactivitybecomesimportantindefiningthetimedependentdecayofATPelevels.ADPeinhibition ofthenon-lyticATPeffluxwasstrong,whereasATPeactivationwasminimal.Finally,the modelwasabletopredicttheconsequencesofpartialinhibitionofecto-ATPaseactivityontheATPekinetic,thusemulatingtheexposureofgoldfishcellstohypotonicmediuminthepresenceoftheATPanalog AMP-PCP.ThemodelpredictsthisanalogtobothinhibitectoATPaseactivityandincreasenon-lytic ATPrelease.
