Wound-induced calcium waves in alveolar type II cells.
Alveolar type II epithelial (ATII) cells repopulate the alveolus after acute lung injury. We hypothesized that injury would initiate signals in nearby survivors. When rat ATII monolayers were wounded, elevations in intracellular free Ca2+ concentration ([Ca2+]i) began at the edge of the wound and propagated outward as a wave for at least 300 microns. The [Ca2+]i wave was due to both influx of extracellular Ca2+ and release of intracellular Ca2+ stores. Reducing Ca2+ influx with brief treatments of ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid or Gd3+ reduced both the amplitude and the apparent speed. Draining intracellular Ca2+ stores by pretreatment with cyclopiazonic acid eliminated the [Ca2+]i wave. Therefore, the [Ca2+]i wave depended critically on intracellular Ca2+ stores. [Ca2+]i elevations propagated over a break in the monolayer, suggesting that extracellular pathways were involved. Furthermore, extracellular factors from injured cells elevated [Ca2+]i in uninjured cultures. We conclude that wounding produces a [Ca2+]i wave in surviving cells and part of this response is mediated by soluble factors released into the extracellular space during injury.
Hinman
L E
LE
Department of Pharmacology, University of Minnesota, Minneapolis 55455, USA.
Beilman
G J
GJ
Groehler
K E
KE
Sammak
P J
PJ
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002478:Cells, Cultured; D004533:Egtazic Acid / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D005682:Gadolinium / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D011650:Pulmonary Alveoli / Q000166:cytology / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014947:Wounds and Injuries
D004791:Enzyme Inhibitors; D007211:Indoles; D004533:Egtazic Acid; D005682:Gadolinium; D000252:Calcium-Transporting ATPases; D002118:Calcium; C000543:cyclopiazonic acid