Compensatory regulation of Cav2.1 Ca2+ channels in cerebellar Purkinje neurons lacking parvalbumin and calbindin D-28k.
Ca(v)2.1 channels regulate Ca(2+) signaling and excitability of cerebellar Purkinje neurons. These channels undergo a dual feedback regulation by incoming Ca(2+) ions, Ca(2+)-dependent facilitation and inactivation. Endogenous Ca(2+)-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 Ca(2+). 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 Ca(2+) 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 Ca(2+) signals in the absence of Ca(2+)-buffering proteins in PV/CB(-/-) Purkinje neurons.
Kreiner
Lisa
L
Department of Molecular Physiology and Biophysics, University of Iowa, 51 Newton Road, Iowa City, IA 52242, USA.
Christel
Carl J
CJ
Benveniste
Morris
M
Schwaller
Beat
B
Lee
Amy
A
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D064026:Calbindins; D002118:Calcium / Q000378:metabolism; D020864:Calcium Channels, N-Type / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D010320:Parvalbumins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D010507:Periodicity; D011689:Purkinje Cells / Q000502:physiology*; D051381:Rats; D064030:S100 Calcium Binding Protein G / Q000235:genetics / Q000378:metabolism*
D064026:Calbindins; D002118:Calcium; D020864:Calcium Channels, N-Type; D010320:Parvalbumins; D064030:S100 Calcium Binding Protein G