Lipid rafts, the sarcoplasmic reticulum and uterine calcium signalling: an integrated approach.
The pathways involved in Ca2+ signalling in the uterus remain incompletely understood, impairing our ability to prevent preterm and difficult labours. In this review we focus on two elements in the pathway of Ca2+ signalling that have recently emerged as playing important roles: membrane lipid rafts and the sarcoplasmic reticulum. We examine the evidence for lipid rafts in the uterus and discuss their functional role. We suggest that the increases in cytosolic [Ca2+] and contractility that occur with raft disruption are due, at least in part, to effects on large conductance Ca2+-activated K+ (BK) channels that are localized to rafts. The role of the SR in contributing to subsarcolemmal cytosolic microdomains in uterus is evaluated, along with its interactions with ion channels on the plasma membrane. Thus, signalling microdomains play an important, but incompletely understood, role in the uterus, and integrating them into other Ca2+ signalling pathways is a challenge for further research. We suggest that the role of the SR changes in pregnancy, from promoting quiescence via BK channels or SR Ca2+ uptake, to promoting Ca2+ entry and contractility at term, and relate data on lipid rafts to clinical outcome in obese pregnant women.
Noble
Karen
K
Department of Physiology, University of Liverpool, Crown Street, Liverpool, L69 3BX, UK.
Zhang
Jie
J
Wray
Susan
S
D000818:Animals; D020013:Calcium Signaling / Q000502:physiology*; D021941:Caveolae / Q000378:metabolism; D005260:Female; D006801:Humans; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism; D021962:Membrane Microdomains / Q000378:metabolism*; D009215:Myometrium / Q000166:cytology / Q000378:metabolism; D009765:Obesity / Q000150:complications / Q000378:metabolism; D007744:Obstetric Labor Complications / Q000378:metabolism; D011247:Pregnancy; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*; D014590:Uterine Contraction / Q000378:metabolism; D014599:Uterus / Q000378:metabolism*
D051036:Large-Conductance Calcium-Activated Potassium Channels