Compensatory Regulation of Ca(v)2.1 Ca2+ Channels in Cerebellar Purkinje Neurons Lacking Parvalbumin and Calbindin D-28k

Kreiner L, Christel CJ, Benveniste M, Schwaller B, Lee A. Compensatory regulation of Ca(v)2.1 Ca2+ channels in cerebellar Purkinje neurons lacking parvalbumin and calbindin D-28k. J Neurophysiol 103: 371-381, 2010. First published November 11, 2009; doi: 10.1152/jn.00635.2009. Ca(v)2.1 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 Ca(v)2.1 regulation by Ca2+. To test this, we compared Ca(v)2.1 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 Ca(v)2.1. Ca(v)2.1 currents in PV/CB-/- neurons exhibited increased voltage-dependent inactivation, which could be traced to decreased expression of the auxiliary Ca-v beta 2a subunit compared with WT neurons. Although Ca(v)2.1 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 Ca(v)2.1 beta-subunits may preserve normal activity-dependent Ca2+ signals in the absence of Ca2+-buffering proteins in PV/CB-/- Purkinje neurons.