Dynamic excitation states and firing patterns are controlled by sodium channel kinetics in myenteric neurons: a simulation study.

Enteric neurons located in the gastro-intestinal tract are of particular importance to control digestive functions such as motility and secretion. In our recent publication, we showed that mouse myenteric neurons exhibit 2 types of tetrodotoxin-resistant Na(+) currents: a fast inactivating Na(+) current produced by Nav1.5 channels, present in nearly all myenteric neurons, and a persistent Na(+) current attributed to Nav1.9 channels, restricted to the intrinsic primary afferent neurons (IPANs). By combination of experimental recording and computer simulation we found that Nav1.5 contributed to the upstroke velocity of action potentials (APs), whereas Nav1.9 opposed AP repolarization. Here, we detailed the Na(+), Ca(2+) and K(+) currents used in our computational model of IPAN. We refined the prototype cell to reproduce the sustained firing pattern recorded in situ. As shown in experimental conditions we demonstrated that Nav1.9 channels critically determine the up-state life-time and thus, are essential to sustain tonic firing.

Heterogeneous synaptic covering and differential charge transfer sensitivity among the dendrites of a reconstructed abducens motor neurone: correlations between electron microscopic and computer simulation data.

Ultrastructural studies on the synaptology of dendritic arborizations of motoneurones have been problematic because dendrites are very thin in relation to their great length, and most of the studies on this topic have therefore dealt with only small parts of the dendritic tree. Here we compared the ultrastructural characteristics of the axon terminals distributed along the various dendrites of a single motoneurone. For this purpose, the light microscopic 3D reconstruction of the dendritic arborization of an intracellularly labelled abducens motoneurone was combined with an electron microscopic analysis of its synaptic contacts. Dendritic profiles were randomly sampled along the various dendrites and the axon terminals they received were classified on the basis of their ultrastructural features and their GABA-immunoreactivity. It emerged that the various dendrites differed according to the type and local arrangement of their synaptic inputs. Our second aim was to incorporate the morphological data obtained into a model giving the charge transfer effectiveness T(x) of the dendritic sites. The sensitivity S(x) of T(x) to changes in the membrane resistivity (Rm) simulating various levels of tonic synaptic activity was calculated. It turned out that both the proximal and distal regions of the dendritic arborization have a dense synaptic covering and a weak sensitivity to changes in the Rm, whereas the intermediate dendrites have a sparse synaptic covering and a high sensitivity to changes in tonic synaptic activity. This pattern of organisation might mediate the "gating" of a population of synapses covering some dendritic regions in a state-dependent fashion.