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Thapsigargin enhances a spreading arteriolar dilation and increases the velocity of the local endothelial intercellular calcium wave
Author(s) -
Crowe William E.,
Sarelius Ingrid H.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a486-c
Subject(s) - thapsigargin , chemistry , calcium , acetylcholine , perfusion , biophysics , vasodilation , intracellular , endocrinology , medicine , anatomy , biology , biochemistry , organic chemistry
Endothelial cell (EC) calcium (Ca) is involved in spreading arteriolar dilations; store depletion with thapsigargin (Th) was used to explore the role of internal Ca stores. Arteriolar ECs in cremaster m . of anesthetized [Nembutal, 65 mg/kg ip] mice were loaded with fluo‐4; blood perfusion was then restored. Application of an acetylcholine pulse [100 μM, 500 ms] induced both local (14 ± 7%, n=5) and remote (>500 μm; 9 ± 5%, n=4) dilations, and invoked a rapid rise in EC Ca (1.9 ± 0.5 F/Fo) followed by a local intercellular Ca wave that propagated at 37.8 ± 3.0 μm/s. With Th (100 nM) present, both the local and remote dilations nearly doubled (26 ± 9%, n=5; 21 ± 10%, n=4; respectively) and local Ca wave velocity increased by ~50% (58.3 ± 4.3 μm/s; 1.9 ± 0.3 F/Fo). Th enhancement of the remote Ca response was complex with three different patterns observed: 59% of the regions decreased (trough: 0.72 ± 0.03 F/Fo, n = 16), 22% increased (peak: 1.29 ± 0.07 F/Fo, n = 6) and c) 19% of the responses were biphasic (trough: 0.82 ± 0.04 F/Fo, peak: 1.24 ± 0.06 F/Fo, n = 5). We conclude that the release of Ca from internal stores is not required for the spreading dilation or local Ca wave but rather Th enhances these processes by stimulating external Ca entry. The complex remote EC Ca response likely reflects enhanced Ca entry that is countered by the activation of a dilation‐dependent Ca sink. [Supported by: HL18208, HL75186, HL 76414]