title: A role for Ca(2+)-conducting ion channels in mechanically-induced signal transduction of airway epithelial cells.
abstract: Mechanical stimulation of a single cell in a cultured monolayer of airway epithelial cells initiates an intercellularly communicated increase in intracellular Ca2+ concentration ([Ca2+]i) that propagates radically through adjacent cells via gap junctions, forming an intercellular Ca2+ wave. Mechanically-induced intercellular Ca2+ waves also occur in the absence of extracellular Ca2+. However, in Ca(2+)-free medium an increase in [Ca2+]i of the stimulated cell does not occur. Thus, mechanically-induced [Ca2+]i changes in the stimulated cell are influenced by the extracellular Ca2+ concentration. To investigate if a channel-mediated Ca2+ flux across the plasma membrane contributes to the elevation of [Ca2+]i in the stimulated cell we used digital image microscopy to measure mechanically-induced [Ca2+]i changes in the presence of Ca2+ channel blockers. In Ca(2+)-free medium containing Gd3+ (20 microM) mechanical stimulation resulted in an [Ca2+]i increase in the stimulated cell. The delay time between mechanical stimulation and increase in [Ca2+]i of the stimulated cell was dependent on extracellular [Gd3+], with a half-maximal effective concentration of approximately 40 microM. Mechanical stimulation in Ca(2+)-free medium containing La3+ (10 microM) or Ni2+ (100 microM) gave similar results. Mechanical stimulation in Ca(2+)-free medium containing the dihydropyridine Ca2+ channel blockers nifedipine (10 microM) and nimodipine (10 microM) also resulted in an increase of [Ca2+]i of the stimulated cell. Mechanical stimulation of cells treated with thapsigargin to deplete intracellular Ca2+ stores, in the presence of 1.3 mM extracellular Ca2+, results in an increase in [Ca2+]i of the stimulated cell without the propagation of an intercellular Ca2+ wave.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Anatomy and Cell Biology, UCLA School of Medicine, University of California 90024-1763.
authors.forename: S
authors.initials: S
authors.lastname: Boitano
authors.forename: M J
authors.initials: MJ
authors.lastname: Sanderson
authors.forename: E R
authors.initials: ER
authors.lastname: Dirksen
mesh_terms: D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D008856:Microscopy, Fluorescence; D009532:Nickel / Q000494:pharmacology; D010812:Physical Stimulation; D011817:Rabbits; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin; D014132:Trachea / Q000187:drug effects / Q000378:metabolism*
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D013729:Terpenes; D019284:Thapsigargin; D009532:Nickel; D002118:Calcium