TY - JOUR
T1 - Altered Neuronal Excitability in Cerebellar Granule Cells of Mice Lacking Calretinin
AU - Gall, David
AU - Roussel, Céline
AU - Susa, Isabella
AU - D'Angelo, Egidio
AU - Rossi, Paola
AU - Bearzatto, Bertrand
AU - Galas, Marie Christine
AU - Blum, David
AU - Schurmans, Stéphane
AU - Schiffmann, Serge N.
PY - 2003/10/15
Y1 - 2003/10/15
N2 - 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.
AB - 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.
KW - Calcium
KW - Calcium-binding protein
KW - Calretinin
KW - Cerebellar granule cell
KW - Excitability
KW - Mathematical model
UR - http://www.scopus.com/inward/record.url?scp=0142250836&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0142250836&partnerID=8YFLogxK
M3 - Article
C2 - 14561859
AN - SCOPUS:0142250836
VL - 23
SP - 9320
EP - 9327
JO - Journal of Neuroscience
JF - Journal of Neuroscience
SN - 0270-6474
IS - 28
ER -