Somatic Ca2+ signaling in cerebellar Purkinje neurons

Activity‐driven Ca2+ signaling plays an important role in a number of neuronal functions, including neuronal growth, differentiation, and plasticity. Both cytosolic and nuclear Ca2+ has been implicated in these functions. In the current study, we investigated membrane‐to‐nucleus Ca2+ signaling in cerebellar Purkinje neurons in culture to gain insight into the pathways and mechanisms that can initiate nuclear Ca2+ signaling in this neuronal type. Purkinje neurons are known to express an abundance of Ca2+ signaling molecules such as voltage‐gated Ca2+ channels, ryanodine receptors, and IP3 receptors. Results show that membrane depolarization evoked by brief stimulation with K+ saline elicits a prominent Ca2+ signal in the cytosol and nucleus of the Purkinje neurons. Ca2+ influx through P/Q‐ and L‐type voltage‐gated Ca2+ channels and Ca2+‐induced Ca2+ release (CICR) from intracellular stores contributed to the Ca2+ signal, which spread from the plasma membrane to the nucleus. At strong K+ stimulations, the amplitude of the nuclear Ca2+ signal exceeded that of the cytosolic Ca2+ signal, suggesting the involvement of a nuclear amplification mechanism and/or differences in Ca2+ buffering in these two cellular compartments. An enhanced nuclear Ca2+ signal was more prominent for Ca2+ signals elicited by membrane depolarization than for Ca2+ signals elicited by activation of the metabotropic glutamate receptor pathway (mGluR1), which is linked to Ca2+ release from intracellular stores controlled by the IP3 receptor. © 2009 Wiley‐Liss, Inc.