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Compensatory Regulation of Cav2.1 Ca²⁺ Channels in Cerebellar Purkinje Neurons Lacking Parvalbumin and Calbindin D-28k

  • Kreiner, Lisa Department of Pharmacology, Emory University, Atlanta, USA
  • Christel, Carl J. Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, USA
  • Benveniste, Morris Neuroscience Institute, Morehouse School of Medicine, Atlanta, USA
  • Schwaller, Beat Department of Medicine, Unit of Anatomy, University of Fribourg, Switzerland
  • Lee, Amy Department of Pharmacology, Emory University, Atlanta, USA - Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, USA
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    11.11.2009
Published in:
  • Journal of Neurophysiology. - 2010, vol. 103, p. 371-381
English 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.
Faculty
Faculté des sciences et de médecine
Department
Département de Médecine
Language
  • English
Classification
Biology
License
License undefined
Identifiers
Persistent URL
https://folia.unifr.ch/unifr/documents/301253
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