Expression and regulation of sodium/calcium exchangers, NCX and NCKX, in reproductive tissues: do they play a critical role in calcium transport for reproduction and development?

Plasma membrane sodium/calcium (Na(+)/Ca(2+)) exchangers are an important component of intracellular calcium [Ca(2+)](i) homeostasis and electrical conduction. Na(+)/Ca(2+) exchangers, NCX and NCKX, play a critical role in the transport of one [Ca(2+)](i) and potassium ion across the cell membrane in exchange for four extracellular sodium ions [Na(+)](e). Mammalian plasma membrane Na(+)/Ca(2+) exchange proteins are divided into two families: one in which Ca(2+) flux is dependent only on sodium (NCX1-3) and another in which Ca(2+) flux is also dependent on potassium (NCKX1-4). Both molecules are capable of forward- and reverse-mode exchange. In cells and tissues, Na(+)/Ca(2+) (and K(+)) gradients localize to the cell membrane; thus, the exchangers transport ions across a membrane potential. Uterine NCKX3 has been shown to be involved in the regulation of endometrial receptivity by [Ca(2+)](i). In the uterus and placenta, NCKX3 expression is regulated by the sex steroid hormone estrogen (E2) and hypoxia stress, respectively. In this chapter, we described the expression and regulation of these proteins for reproductive functions in various tissues including uterus, placenta, and kidney of humans and rodents. Evidence to date suggests that NCKX3 and NCX1 may be regulated in a tissue-specific manner. In addition, we focused on the molecular mechanism involved in the regulation of NCKX3 and NCX1 in mammals, based upon our recent results and those of others.