Understanding the mechanisms regulating contractions in the myometrium during pregnancy may help avoid scenarios such as premature births. During labor, increases in intracellular calcium (Ca2+) are closely correlated with human myometrium contractions. Potential ion channels responsible for Signal-Regulated Ca2+ Entry (SRCE) are the canonical type of transient receptor potential (TrpC) channels, postulated to form hetero- or homotetramers thus, allowing formation of a variety of channels possessing different physiological properties. Our main objective is to understand the functional roles of specific TrpC proteins in relation to Ca2+ signaling to elucidate their relative significance in myometrium.
Specific aims 1) To study the contribution of hTrpC4 to Ca2+ dynamics in human myometrium, 2) To determine the function of hTrpd on Ca2+ dynamics in human myometrium, 3) To determining the effect of hTrpC4 plus hTrpd knockdown in human myometrium.
Specific aims will be studied by the use of gene silencing experiments to induce knockdown of the specific TrpC proteins. Effects will then be studied by measuring Ca2+ levels using Fura-2 fluorescent Ca2+ indicator.
Murtazina, Dilyara A; Chung, Daesuk; Ulloa, Aida et al. (2011) TRPC1, STIM1, and ORAI influence signal-regulated intracellular and endoplasmic reticulum calcium dynamics in human myometrial cells. Biol Reprod 85:315-26 |
Ulloa, Aida; Gonzales, Albert L; Zhong, Miao et al. (2009) Reduction in TRPC4 expression specifically attenuates G-protein coupled receptor-stimulated increases in intracellular calcium in human myometrial cells. Cell Calcium 46:73-84 |