[Ca2+]i regulates transcription rate of the Na+/K(+)-ATPase alpha 1 subunit

The Na+/K(+)-ATPase enzyme is a pivotal regulator of intracellular electrolyte levels in animal cells. Changes in the rate of its synthesis have been demonstrated to mediate a number of physiological responses. The cellular mechanisms implicated in such regulatory responses though remain poorly defined. Specifically, no intracellular mediators have previously been established. We now describe for the first time, one putative mediator: [Ca2+]i. Elevations in [Ca2+]i stimulate levels of mRNA alpha 1 and mRNA beta 1, sequences which encode both the catalytic subunit of the enzyme, the alpha subunit, and the glycosylated subunit, the beta subunit. These results suggest that elevations in [Ca2+]i modulate the synthetic rate of the active enzyme, and consequently changes in [Ca2+]i may mediate the regulation of its synthetic rate in a range of physiological settings. The mRNA alpha 1 response to the elevation of [Ca2+]i appears, at least partly, to reflect an increase in transcription rate. However, no such increase in transcription rate of the beta 1 subunit gene was detectable. Thus the mRNA beta 1 response, under conditions of elevated [Ca2+]i, may be explained by a decrease in specific mRNA degradation rate.