Pregnancy-adapted uterine artery endothelial cell Ca2+ signaling and its relationship with membrane potential.

Bikash Pattnaik // Publications // Nov 01 2017

PubMed ID: 29122954

Author(s): Alvarez RE, Boeldt DS, Pattnaik BR, Friedman HL, Bird IM. Pregnancy-adapted uterine artery endothelial cell Ca2+ signaling and its relationship with membrane potential. Physiol Rep. 2017 Nov;5(21). pii: e13452. doi: 10.14814/phy2.13452. PMID 29122954

Journal: Physiological Reports, Volume 5, Issue 21, Nov 2017

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 (TRPC3) and inositol 1,4,5-triphosphate receptor type 2 (IP3R2), which is upregulated in P-UAEC in a manner dependent on connexin 43 (Cx43) gap junctions. While there is no known direct interaction of TRPC3 with Cx43, early descriptions of TRPC3 function showed it may also be influenced by altered membrane potential (Vm). Herein, we ask if enhanced TRPC3 Ca2+ bursting due to enhanced Cx43 coupling may be coupled via dynamic alterations in Vm 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 Vm 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, Vm is not coregulated with any periodicity related to [Ca2+]i bursting. Only a small but significant progressive change in Vm 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.

© 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.