calretinin; calcium-binding protein; cerebellar granule cell; excitability; calcium; mathematical model
Abstract :
[en] Calcium-binding proteins such as calretinin are abundantly expressed in distinctive patterns in the CNS, but their physiological function remains poorly understood. Calretinin is expressed in cerebellar granule cells, which provide the major excitatory input to Purkinje cells through parallel fibers. Calretinin-deficient mice exhibit dramatic alterations in motor coordination and Purkinje cell firing recorded in vivo through unknown mechanisms. In the present study, we used patch-clamp recording techniques in acute slice preparation to investigate the effect of a null mutation of the calretinin gene on the intrinsic electroresponsiveness of cerebellar granule cells at a mature developmental stage. Calretinin-deficient granule cells exhibit faster action potentials and generate repetitive spike discharge showing an enhanced frequency increase with injected currents. These alterations disappear when 0.15 mm of the exogenous fast-calcium buffer BAPTA is infused in the cytosol to restore the calcium-buffering capacity. A proposed mathematical model demonstrates that the observed alterations of granule cell excitability can be explained by a decreased cytosolic calcium-buffering capacity resulting from the absence of calretinin. This result suggests that calcium-binding proteins modulate intrinsic neuronal excitability and may therefore play a role in information processing in the CNS
Gall, D.; Université Libre de Bruxelles - ULB > Laboratoire de Neurophysiologie (CP601), Faculté de Médecine
Roussel, C.; Université Libre de Bruxelles - ULB > Laboratoire de Neurophysiologie (CP601), Faculé de Médecine
Susa, I.; Université Libre de Bruxelles - ULB > Optique Nonlinéaire Théorique (CP231), Faculté des Sciences
D’Angelo, E.; University of Pavia and Instituto Nazionale per la Fisica della Materia, I-27100 Pavia, Italy > Department of Cellular and Molecular Physiology and Pharmacology
Rossi, P.; University of Pavia and Instituto Nazionale per la Fisica della Materia, I-27100 Pavia, Italy > Department of Cellular and Molecular Physiology and Pharmacology
Bearzatto, B.; Université Libre de Bruxelles - ULB > Laboratoire de Neurophysiologie (CP601), Faculté de Médecine
Galas, M. C.; Université Libre de Bruxelles - ULB > Laboratoire de Neurophysiologie (CP601), Faculté de Médecine
Blum, D.; Université Libre de Bruxelles - ULB > Laboratoire de Neurophysiologie (CP601), Faculté de Médecine
Schurmans, Stéphane ; Université de Liège - ULiège > Département de sciences fonctionnelles > Biochimie métabolique vétérinaire
Schiffmann, S. N.; Université Libre de Bruxelles - ULB > Laboratoire de Neurophysiologie (CP601), Faculté de Médecine
Language :
English
Title :
Altered neuronal excitability in cerebellar granule cells of mice lacking calretinin
Publication date :
2003
Journal title :
Journal of Neuroscience
ISSN :
0270-6474
eISSN :
1529-2401
Publisher :
Society for Neuroscience, Washington, United States - District of Columbia
Volume :
23
Issue :
28
Pages :
9320-9327
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
This work was supported by the Belgian Fonds pour la Recherche dans l’Industrie et l’Agriculture (C.R., B.B.), Queen Elisabeth Medical Foundation (Neurobiology 99-01 and 02-04), Fund for Medical Scientific Research (Belgium 3.4551.98/3.4507.02), Fondation David et Alice Van Buren, Action de Recherche Concerte´e (2002-2005), and the European Commission’s Fifth Framework Program for Research (Cerebellum BIO4CT98-0182 and Spikeforce IST35271)
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