Dissociated Hippocampal Neurons Exhibit Distinct Zn Dynamics in a Stimulation-Method-Dependent Manner.

Ionic Zn has increasingly been recognized as an important neurotransmitter and signaling ion in glutamatergic neuron pathways. Intracellular Zn transiently increases as a result of neuronal excitation, and this Zn signal is essential for neuron plasticity, but the source and regulation of the signal is still unclear. In this study, we rigorously quantified Zn, Ca, and pH dynamics in dissociated mouse hippocampal neurons stimulated with bath application of high KCl or glutamate. While both stimulation methods yielded Zn signals, Ca influx, and acidification, glutamate stimulation induced more sustained high intracellular Ca and a larger increase in intracellular Zn. However, the stimulation-induced pH change was similar between conditions, indicating that a different cellular change is responsible for the stimulation-dependent difference in Zn signal. This work provides the first robust quantification of Zn dynamics in neurons using different methods of stimulation.