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Essential role for calcium waves in migration of human vascular smooth muscle cells
Author(s) -
EspinosaTanguma Ricardo,
O’Neil Caroline,
Pickering Geoffrey J,
Sims Stephen M
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.21.6.a1441-a
Vascular smooth muscle cells (SMC) exhibit diversity in phenotypes, and have the capacity to convert from a contractile to a synthetic phenotype in response to injury or remodeling. Cells with a synthetic phenotype have the ability to migrate. SMC migration is initiated at the leading edge of cells with lamellipodial extension and attachment to substrate, coupled with release of the rear (uropod) of the cell, enabling forward movement. However, little is known regarding the role of cytosolic Ca 2+ in coordinating the disparate activities of migrating SMCs. Our aim was to investigate regional changes of Ca 2+ in human vascular SMC using digital fluorescence microscopy of fura‐2 loaded cells. SMCs exhibited spontaneous Ca 2+ waves, and stimulation with PDGF caused transient global rise of [Ca 2+ ]. Ca 2+ waves characteristically swept from the rear of polarized cells towards the leading edge. To investigate the role of Ca 2+ waves in initiating retraction, we loaded cells with the Ca 2+ chelator BAPTA, which abolished Ca 2+ waves and cell migration. In contrast, BAPTA loading caused negligible change in lamellipod motility. Treatment of cells with the Ca 2+ channel blocker nifedipine did not noticeably alter cell motility. These results identify a novel mechanism by which SMC migration occurs, whereby release of the uropod is initiated by regional changes of cytosolic Ca 2+ and waves. Supported by CIHR to SMS and PIFI 3.1 to RET.