Somatic Ca2+ signaling in cerebellar Purkinje neurons

Activity-driven Ca(2+) signaling plays an important role in a number of neuronal functions, including neuronal growth, differentiation, and plasticity. Both cytosolic and nuclear Ca(2+) has been implicated in these functions. In the current study, we investigated membrane-to-nucleus Ca(2+) signaling in cerebellar Purkinje neurons in culture to gain insight into the pathways and mechanisms that can initiate nuclear Ca(2+) signaling in this neuronal type. Purkinje neurons are known to express an abundance of Ca(2+) signaling molecules such as voltage-gated Ca(2+) channels, ryanodine receptors, and IP3 receptors. Results show that membrane depolarization evoked by brief stimulation with K(+) saline elicits a prominent Ca(2+) signal in the cytosol and nucleus of the Purkinje neurons. Ca(2+) influx through P/Q- and L-type voltage-gated Ca(2+) channels and Ca(2+)-induced Ca(2+) release (CICR) from intracellular stores contributed to the Ca(2+) signal, which spread from the plasma membrane to the nucleus. At strong K(+) stimulations, the amplitude of the nuclear Ca(2+) signal exceeded that of the cytosolic Ca(2+) signal, suggesting the involvement of a nuclear amplification mechanism and/or differences in Ca(2+) buffering in these two cellular compartments. An enhanced nuclear Ca(2+) signal was more prominent for Ca(2+) signals elicited by membrane depolarization than for Ca(2+) signals elicited by activation of the metabotropic glutamate receptor pathway (mGluR1), which is linked to Ca(2+) release from intracellular stores controlled by the IP3 receptor.