title: Oscillations of pH inside the secretory granule control the gain of Ca2+ release for signal transduction in goblet cell exocytosis.
abstract: Although Ca2+ plays a critical function in relaying intracellular messages, the role of subcellular organelles in the dynamics of intracellular Ca2+ still remains largely unexplored. We recently demonstrated that secretory granules can signal their own export from the cell by releasing Ca2+ to the cytosol. Oscillations and release of Ca2+ in/from the granule result from the combined action of a Ca2+/K+ ion exchange process that occurs in the granule's matrix, and the sequential activation of two Ca2+-sensitive ion channels: an inositol 1,4,5-trisphosphate receptor Ca2+ channel (InsP3R) and an apamin-sensitive Ca2+-activated K+ channel (ASK(Ca)). The results reported here from studies using isolated mucin granules indicate that intralumenal granular Ca2+ oscillations ([Ca2+]L) and the corresponding cyclical release of Ca2+ to the cytosol induced by InsP3 are accompanied by corresponding intragranular pH(G) oscillations. Our data show that K+-induced unbinding of Ca2+ from the mucin matrix increases as the pH(G) declines. These observations suggest that oscillations of pH(G) can modulate the gain of the Ca2+/K+ ion exchange process, thereby controlling the amplitude of [Ca2+]L oscillations and the granule-cytosol release gradient of [Ca2+].
authors.affiliation: Department of Bioengineering, University of Washington, Seattle, WA 98195, USA.
authors.forename: Wei-chun
authors.initials: WC
authors.lastname: Chin
authors.forename: Ivan
authors.initials: I
authors.lastname: Quesada
authors.forename: Thuc
authors.initials: T
authors.lastname: Nguyen
authors.forename: Pedro
authors.initials: P
authors.lastname: Verdugo
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D003594:Cytoplasmic Granules / Q000737:chemistry*; D005088:Exocrine Glands / Q000166:cytology* / Q000378:metabolism; D005089:Exocytosis / Q000502:physiology*; D006863:Hydrogen-Ion Concentration; D015544:Inositol 1,4,5-Trisphosphate / Q000502:physiology; D053496:Inositol 1,4,5-Trisphosphate Receptors; D017136:Ion Transport / Q000187:drug effects / Q000502:physiology; D046911:Macromolecular Substances; D008954:Models, Biological; D009077:Mucins / Q000378:metabolism; D009093:Mucus / Q000378:metabolism*; D024681:Potassium Channels, Calcium-Activated / Q000502:physiology; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology
chemical_list: D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D046911:Macromolecular Substances; D009077:Mucins; D024681:Potassium Channels, Calcium-Activated; D018160:Receptors, Cytoplasmic and Nuclear; D015544:Inositol 1,4,5-Trisphosphate