Attenuation of canonical transient receptor potential-like channel 6 expression specifically reduces the diacylglycerol-mediated increase in intracellular calcium in human myometrial cells.

Endocrinology
Daesuk ChungBarbara M Sanborn

Abstract

An increase in intracellular Ca(2+) ([Ca(2+)](i)) as a result of release of Ca(2+) from intracellular stores or influx of extracellular Ca(2+) contributes to the regulation of smooth muscle contractile activity. Human uterine smooth muscle cells exhibit receptor-, store-, and diacylglycerol (OAG)-mediated extracellular Ca(2+)-dependent increases in [Ca(2+)](i) (SRCE) and express canonical transient receptor potential-like channels (TRPC) mRNAs (predominantly TRPC1, -4, and -6) that have been implicated in SRCE. To determine the role of TRPC6 in human myometrial SRCE, short hairpin RNA constructs were designed that effectively targeted a TRPC6 mRNA reporter for degradation. One sequence was used to produce an adenovirus construct (TC6sh1). TC6sh1 reduced TRPC6 mRNA but not TRPC1, -3, -4, -5, or -7 mRNAs in PHM1-41 myometrial cells. Compared with uninfected cells or cells infected with empty vector, the increase in [Ca(2+)](i) in response to OAG was specifically inhibited by TC6sh1, whereas SRCE responses elicited by either oxytocin or thapsigargin were not changed. Similar findings were observed in primary pregnant human myometrial cells. When PHM1-41 cells were activated by OAG in the absence of extracellular Na(+), the increas...Continue Reading

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Citations

Feb 3, 2011·American Journal of Obstetrics and Gynecology·Pooja MittalSonia S Hassan
Jun 14, 2018·Physiological Reviews·Benjamin Jurek, Inga D Neumann
Jul 31, 2013·Journal of Perinatal Medicine·Piya ChaemsaithongTinnakorn Chaiworapongsa
Aug 8, 2020·European Journal of Pharmacology·Julia ScheubleGerald Thiel
Sep 28, 2021·The Journal of Obstetrics and Gynaecology Research·Ícaro Araújo de SousaFrancisco Chagas Filho

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