title: Hindered cytoplasmic diffusion of inositol trisphosphate restricts its cellular range of action.
abstract: The range of action of intracellular messengers is determined by their rates of diffusion and degradation. Previous measurements in oocyte cytoplasmic extracts indicated that the Ca2+-liberating second messenger inositol trisphosphate (IP3) diffuses with a coefficient (~280 μm2s-1) similar to that in water, corresponding to a range of action of ~25 μm. Consequently, IP3is generally considered a "global" cellular messenger. We reexamined this issue by measuring local IP3-evoked Ca2+puffs to monitor IP3diffusing from spot photorelease in neuroblastoma cells. Fitting these data by numerical simulations yielded a diffusion coefficient (≤10 μm2s-1) about 30-fold slower than that previously reported. We propose that diffusion of IP3in mammalian cells is hindered by binding to immobile, functionally inactive receptors that were diluted in oocyte extracts. The predicted range of action of IP3(<5 μm) is thus smaller than the size of typical mammalian cells, indicating that IP3should better be considered as a local rather than a global cellular messenger.
authors.affiliation: Department of Neurobiology and Behavior, University of California, Irvine, CA 92697, USA. dickinsg@uci.edu.
authors.forename: George D
authors.initials: GD
authors.lastname: Dickinson
authors.affiliation: Department of Neurobiology and Behavior, University of California, Irvine, CA 92697, USA.
authors.forename: Kyle L
authors.initials: KL
authors.lastname: Ellefsen
authors.affiliation: Departamento de Física, FCEN-UBA and IFIBA, CONICET, Buenos Aires, Argentina.
authors.forename: Silvina Ponce
authors.initials: SP
authors.lastname: Dawson
authors.affiliation: Theoretical Biology and Biophysics, T-10 MS K710, Los Alamos National Laboratory, Los Alamos, NM 87545, USA.
authors.forename: John E
authors.initials: JE
authors.lastname: Pearson
authors.affiliation: Department of Neurobiology and Behavior, University of California, Irvine, CA 92697, USA.|Department of Physiology and Biophysics, University of California, Irvine, CA 92697, USA.
authors.forename: Ian
authors.initials: I
authors.lastname: Parker
mesh_terms: D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D045744:Cell Line, Tumor; D003593:Cytoplasm / Q000378:metabolism*; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D009447:Neuroblastoma / Q000378:metabolism*
chemical_list: D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium