Altered neuronal excitability in cerebellar granule cells of mice lacking calretinin.
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
David
D
Laboratoire de Neurophysiologie (CP601), Faculté deMédecine, Université Libre de Bruxelles, B-1070 Bruxelles, Belgium.
Roussel
Céline
C
Susa
Isabella
I
D'Angelo
Egidio
E
Rossi
Paola
P
Bearzatto
Bertrand
B
Galas
Marie Christine
MC
Blum
David
D
Schurmans
Stéphane
S
Schiffmann
Serge N
SN
D000818:Animals; D002021:Buffers; D064032:Calbindin 2; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D002462:Cell Membrane / Q000502:physiology; D002531:Cerebellum / Q000166:cytology / Q000502:physiology*; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D066298:In Vitro Techniques; D007478:Iontophoresis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008959:Models, Neurological; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D018408:Patch-Clamp Techniques; D064030:S100 Calcium Binding Protein G / Q000235:genetics* / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology
D002021:Buffers; C576511:Calb2 protein, mouse; D064032:Calbindin 2; D064030:S100 Calcium Binding Protein G; D002118:Calcium