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.