Cav2.1 channels regulate Ca2+ signaling and excitability of cerebellar Purkinje neurons. These channels undergo a dual feedback regulation by incoming Ca2+ ions, Ca2+-dependent facilitation and inactivation. Endogenous Ca2+-buffering proteins, such as parvalbumin (PV) and calbindin D-28k (CB), are highly expressed in Purkinje neurons and therefore may influence Cav2.1 regulation by Ca2+. To test this, we compared Cav2.1 properties in dissociated Purkinje neurons from wild-type (WT) mice and those lacking both PV and CB (PV/CB−/−). Unexpectedly, P-type currents in WT and PV/CB−/− neurons differed in a way that was inconsistent with a role of PV and CB in acute modulation of Ca2+ feedback to Cav2.1. Cav2.1 currents in PV/CB−/− neurons exhibited increased voltage-dependent inactivation, which could be traced to decreased expression of the auxiliary Cavβ2a subunit compared with WT neurons. Although Cav2.1 channels are required for normal pacemaking of Purkinje neurons, spontaneous action potentials were not different in WT and PV/CB−/− neurons. Increased inactivation due to molecular switching of Cav2.1 β-subunits may preserve normal activity-dependent Ca2+ signals in the absence of Ca2+-buffering proteins in PV/CB−/− Purkinje neurons.
Subcellular structural plasticity caused by the absence of the fast Ca2+ buffer calbindin D-28k in recurrent collaterals of cerebellar Purkinje neurons