Rôle du Ca2+ dans la propriété de type pacemaker des motoneurones spinaux

Abstract

Cet article porte sur les mécanismes ioniques associés à l’expression de la propriété pacemaker qui ont pour véhicules les motoneurones de la région lombaire de la moelle épinière. L’attention porte en particulier sur les mécanismes liés au Ca2+, puisqu’ils n’ont attiré que peu d’intérêt jusqu’ici comparativement aux autres mécanismes ioniques tels que ceux liés au Na2+, K+, Mg2+… La mise en perspective de données récentes, dont certaines proviennent de nos travaux, contribue à éclaircir le rôle à la fois complexe et déterminant des courants et mécanismes calciques sous-jacents à cette propriété neuronale singulière. Ces résultats devraient permettre de mieux comprendre les mécanismes qui concourent à la composante rythmique de la locomotion, et dont on a clairement établi qu’ils sont localisés au sein de circuits neuronaux lombaires de la moelle épinière.

It is generally accepted that locomotion in vertebrate species is produced by signals coded and integrated by neurons of the spinal cord. In fact, the basic features of locomotion, including patterns and rhythms, are generated by a network of neurons called the CPG (central pattern generator) essentially localized in the lumbar segments of the spinal cord. However, the detailed mechanisms underlying the rhythmic aspect of CPGgenerated locomotion are not fully understood. Here, we report data of studies that focus on the role of Ca2+-related mechanisms involved in the expression of the pacemaker property of lumbar motoneurons that innervate the hindlimbs. In fact, it has become increasingly clear that Ca2+ plays a determinant function in the expression of this active and conditional rhythmic property. In addition to NMDA-mediated currents (NMDA is an agonist of the calcium permeable ionotropic glutamatergic receptor) and to a Ca2+ -dependent K+ current that were found twenty years ago to contribute to intrinsic voltage oscillations in motoneurons, a pivotal role for voltage-gated channels (e.g., CaV1.3) and intracellular Ca2+ concentrations ([Ca2+]i) have recently been shown. Increasing evidence of a role for metabotropic receptor subtypes, calmodulin (a calcium binding protein), ryanodine and IP3-sensitive intracellular stores of Ca2+ suggests that additional mechanisms are yet to be identified. A detailed understanding of the complex role of Ca2+ in mediating the autorhythmic property of spinal neurons may contribute to the development of novel therapeutic approaches to induce locomotion after spinal cord injury.