In April 2016 Manchester eScholar was replaced by the University of Manchester’s new Research Information Management System, Pure. In the autumn the University’s research outputs will be available to search and browse via a new Research Portal. Until then the University’s full publication record can be accessed via a temporary portal and the old eScholar content is available to search and browse via this archive.

Inositol trisphosphate receptor calcium release is required for cerebral artery smooth muscle cell proliferation.

Wilkerson M, Heppner T, Bonev A, Nelson MT

American Journal of Physiology-Heart and Circulatory Physiology. 2006;290( 1):H240-7.

Access to files

Full-text and supplementary files are not available from Manchester eScholar. Use our list of Related resources to find this item elsewhere. Alternatively, request a copy from the Library's Document supply service.

Abstract

Vascular damage signals smooth muscle cells to proliferate, often exacerbating existing pathologies. Although the role of changes in "global" Ca2+ in vascular smooth muscle (VSM) cell dedifferentiation has been studied, the role of specific Ca2+ signals in determining VSM phenotype remains relatively unexplored. Earlier work with cultured VSM cells suggests that inositol 1,4,5-trisphosphate receptor (IP3R) expression and sarcoplasmic reticulum (SR) Ca2+ release may be linked to VSM cell proliferation in native tissue. Thus we hypothesized that SR Ca2+ release through IP3Rs in the form of discrete transient signals is necessary for VSM cell proliferation. To investigate this hypothesis, we used mouse cerebral arteries to design an organ culture system that permitted examination of Ca2+ dynamics in native tissue. Explanted arteries were cultured in normal medium with 10% FBS, and appearance of individual VSM cells migrating from explanted arteries (outgrowth cells) was tracked daily. Initial exposure to 10% FBS increased Ca2+ waves in myocytes in the arteries that were blocked by the IP3R antagonist 2-aminoethoxydiphenylborate (2-APB). Inhibition of IP3R opening (via 100 microM 2-APB, 10 microM xestospongin C, or 25 microM U-73122) dramatically reduced outgrowth cell number compared with untreated or ryanodine-treated (10 microM) arteries. Consistent with this finding, 2-APB inhibited cell proliferation, as measured by reduced proliferating cell nuclear antigen immunostaining within 48 h of culture but did not inhibit cell migration. These results indicate that activation of IP3R Ca2+ release is required for VSM cell proliferation in these arteries.

Bibliographic metadata

Type of resource:
Content type:
Publication type:
Publication form:
Published date:
ISSN:
Place of publication:
United States
Volume:
290( 1)
Start page:
H240
End page:
7
Pagination:
H240-7
Access state:
Active

Institutional metadata

University researcher(s):

Record metadata

Manchester eScholar ID:
uk-ac-man-scw:1d16354
Created:
30th August, 2009, 13:55:32
Last modified:
3rd March, 2010, 17:03:51

Can we help?

The library chat service will be available from 11am-3pm Monday to Friday (excluding Bank Holidays). You can also email your enquiry to us.