NUCLEAR CALCIUM DYNAMICS IN HIPPOCAMPAL NEURONS

Abstract

Increasing evidence points to neuronal nuclear calcium signalling as a conduit between electrical activity and transcription-dependent changes, and it is possible that different mechanisms of nuclear calcium influx trigger distinct genomic responses. Therefore, detailed analysis of these mechanisms is a critical step in understanding nuclear calcium function. We imaged spontaneous cytosolic and nuclear calcium transients and found that nuclear transients decay more slowly, facilitating calcium build-up in the nucleus more readily during rapid trains of transients. To determine whether nuclear transients were dependent on perinuclear calcium release, we inactivated sarco/endoplasmic reticulum calcium ATPase (SERCA) pumps, ryanodine receptors (RyRs) and IP3 receptors (IP3Rs), and found that these manipulations did not have an effect, indicating that nuclear elevations were driven primarily by diffusion of cytosolic calcium through nuclear pores. Finally, by blocking IP3R activation, we demonstrated that RyRs can propagate calcium waves to the nucleus independent of IP3Rs.