In:
American Journal of Physiology-Heart and Circulatory Physiology, American Physiological Society, Vol. 300, No. 6 ( 2011-06), p. H2016-H2026
Abstract:
Phosphoinositide (3,5)-bisphosphate [PI(3,5)P 2 ] is a newly identified phosphoinositide that modulates intracellular Ca 2+ by activating ryanodine receptors (RyRs). Since the contractile state of arterial smooth muscle depends on the concentration of intracellular Ca 2+ , we hypothesized that by mobilizing sarcoplasmic reticulum (SR) Ca 2+ stores PI(3,5)P 2 would increase intracellular Ca 2+ in arterial smooth muscle cells and cause vasocontraction. Using immunohistochemistry, we found that PI(3,5)P 2 was present in the mouse aorta and that exogenously applied PI(3,5)P 2 readily entered aortic smooth muscle cells. In isolated aortic smooth muscle cells, exogenous PI(3,5)P 2 elevated intracellular Ca 2+ , and it also contracted aortic rings. Both the rise in intracellular Ca 2+ and the contraction caused by PI(3,5)P 2 were prevented by antagonizing RyRs, while the majority of the PI(3,5)P 2 response was intact after blockade of inositol (1,4,5)-trisphosphate receptors. Depletion of SR Ca 2+ stores with thapsigargin or caffeine and/or ryanodine blunted the Ca 2+ response and greatly attenuated the contraction elicited by PI(3,5)P 2 . The removal of extracellular Ca 2+ or addition of verapamil to inhibit voltage-dependent Ca 2+ channels reduced but did not eliminate the Ca 2+ or contractile responses to PI(3,5)P 2 . We also found that PI(3,5)P 2 depolarized aortic smooth muscle cells and that LaCl 3 inhibited those aspects of the PI(3,5)P 2 response attributable to extracellular Ca 2+ . Thus, full and sustained aortic contractions to PI(3,5)P 2 required the release of SR Ca 2+ , probably via the activation of RyR, and also extracellular Ca 2+ entry via voltage-dependent Ca 2+ channels.
Type of Medium:
Online Resource
ISSN:
0363-6135
,
1522-1539
DOI:
10.1152/ajpheart.01011.2010
Language:
English
Publisher:
American Physiological Society
Publication Date:
2011
detail.hit.zdb_id:
1477308-9
SSG:
12
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