Shaped by leaky ER: Homeostatic Ca(2+) fluxes

At any moment in time, cells coordinate and balance their calcium ion (Ca(2+)) fluxes. The term ‘Ca(2+) homeostasis’ suggests that balancing resting Ca(2+) levels is a rather static process. However, direct ER Ca(2+) imaging shows that resting Ca(2+) levels are maintained by surprisingly dynamic Ca(2+) fluxes between the ER Ca(2+) store, the cytosol, and the extracellular space. The data show that the ER Ca(2+) leak, continuously fed by the high-energy consuming SERCA, is a fundamental driver of resting Ca(2+) dynamics. Based on simplistic Ca(2+) toolkit models, we discuss how the ER Ca(2+) leak could contribute to evolutionarily conserved Ca(2+) phenomena such as Ca(2+) entry, ER Ca(2+) release, and Ca(2+) oscillations.