Open AccessPregnancy‐adapted uterine artery endothelial cell Ca2+ signaling and its relationship with membrane potential
Author(s) -
Alvarez Roxanne E.,
Boeldt Derek S.,
Pattnaik Bikash R.,
Friedman Hannah L.,
Bird Ian M.
Publication year - 2017
Publication title -
physiological reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 39
ISSN - 2051-817X
DOI - 10.14814/phy2.13452
Subject(s) - trpc , bursting , transient receptor potential channel , gap junction , connexin , coupling (piping) , microbiology and biotechnology , chemistry , receptor , ion channel , medicine , endocrinology , biophysics , biology , neuroscience , materials science , intracellular , metallurgy
Pregnancy‐derived uterine artery endothelial cells (P‐ UAEC ) express P2Y2 receptors and at high cell density show sustained and synchronous [Ca2+]i burst responses in response to ATP . Bursts in turn require coupling of transient receptor potential canonical type3 channel ( TRPC 3) and inositol 1,4,5‐triphosphate receptor type 2 ( IP 3R2), which is upregulated in P‐ UAEC in a manner dependent on connexin 43 (Cx43) gap junctions. While there is no known direct interaction of TRPC 3 with Cx43, early descriptions of TRPC 3 function showed it may also be influenced by altered membrane potential ( V m ). Herein, we ask if enhanced TRPC 3 Ca2+ bursting due to enhanced Cx43 coupling may be coupled via dynamic alterations in V m in P‐ UAEC , as reported in some ( HUVEC ) but not all endothelial cells. Following basic electrical characterization of UAEC , we employed a high sensitivity cell imaging system to simultaneously monitor cell V m and [Ca2+]i in real time in continuous monolayers of UAEC . Our findings show that while acute and sustained phase [Ca2+]i bursting occur dose‐dependently in response to ATP , V m is not coregulated with any periodicity related to [Ca2+]i bursting. Only a small but significant progressive change in V m is seen, and this is more closely related to overall mobilization of Ca2+. Surprisingly, this is also most apparent in NP ‐ UAEC > P‐ UAEC . In contrast [Ca2+]i bursting is more synchronous in P‐ UAEC and even achieves [Ca2+]i waves passing through the P‐ UAEC monolayer. The relevance of these findings to mechanisms of pregnancy adaptation and its failure in hypertensive pregnancy are discussed.