Estimates of the Location of L-type Ca²⁺ Channels in Motoneurons of Different Sizes: A Computational Study

Abstract

In the presence of monoamines, L-type Ca 2+ channels on the dendrites of motoneurons contribute to persistent inward currents (PICs) that can amplify synaptic inputs two-to sixfold. However, the exact location of the L-type Ca 2+ channels is controversial, and the importance of the location as a means of regulating the input-output properties of motoneurons is unknown. In this study, we used a computational strategy developed previously to estimate the dendritic location of the L-type Ca 2+ channels and test the hypothesis that the location of L-type Ca 2+ channels varies as a function of motoneuron size. Compartmental models were constructed based on dendritic trees of five motoneurons that ranged in size from small to large. These models were constrained by known differences in PIC activation reported for low-and high-conductance motoneurons and the relationship between somatic PIC threshold and the presence or absence of tonic excitatory or inhibitory synaptic activity. Our simulations suggest that L-type Ca 2+ channels are concentrated in hotspots whose distance from the soma increases with the size of the dendritic tree. Moving the hotspots away from these sites (e.g., using the hotspot locations from large motoneurons on intermediate-sized motoneurons) fails to replicate the shifts in PIC threshold that occur experimentally during tonic excitatory or inhibitory synaptic activity. In models equipped with a size-dependent distribution of L-type Ca 2+ channels, the amplification of synaptic current by PICs depends on motoneuron size and the location of the synaptic input on the dendritic tree.

Staircase Currents in Motoneurons: Insight into the Spatial Arrangement of Calcium Channels in the Dendritic Tree

“…Using computational models, stepwise repolarizations from Ca 2ϩ plateaus in those neurons were attributed to the independent deactivation of L-type Ca 2ϩ channels at electrotonically segregated "hot spots." Several computational studies using motoneuron models have come to a similar conclusion: functional Ca V 1.3 channels in motoneurons are distributed in segregated regions of the dendritic tree (Bui et al, 2006;Elbasiouny et al, 2006;Grande et al, 2007a).…”

“…These currents are thought to arise from unclamped membrane (i.e., dendrites) and correlate with immunohistochemical evidence of ␣ 1 1.3 subunits in clusters along the dendrites (Carlin et al, 2000;Simon et al, 2003;Ballou et al, 2006). Furthermore, the possibility that the channels mediating PICs are distributed in spatially segregated regions of the dendritic tree of spinal motoneurons has been hypothesized by both computational (Elbasiouny et al, 2006;Grande et al, 2007a) and electrophysiological studies. For example, Heckman and Lee (1999) demonstrated the presence of synaptic amplification on a background of ongoing bistable firing.…”

“…Several dendritic distributions patterns were explored for the Ca V 1.3 channels (Bui et al, 2006;Elbasiouny et al, 2006;Grande et al, 2007a). The conductance of the Ca V 1.3 channels g L,Ca was modeled as follows:…”

“…The fact that the individual stairs are recruited at different times suggests some aspect of spatial asymmetry in their distribution. Several studies have suggested that Ca V 1.3 channels are localized in clusters distributed at varying distances from the cell body (Carlin et al, 2000;Bui et al, 2006;Elbasiouny et al, 2006;Grande et al, 2007a). Therefore, we generated compartmental models consisting of a soma and seven three-compartment primary dendrites, only two of which contained clusters of Ca V 1.3 channels (Fig.…”

Differential contributions of somatic and dendritic calcium-dependent potassium currents to the control of motoneuron excitability following spinal cord injury

“…The L-type calcium PIC, I CaL is likely mediated by low-threshold Cav1.3 calcium channels that are located in the dendrites (Simon et al 2003;Ballou et al 2006;Carlin et al 2000). Previous modeling reports further support a dendritic origin of the plateau-mediating I CaL that reproduced several experimentally observed motoneuron firing properties such as membrane bistability and I-f hysteresis (e.g., (Booth and Rinzel 1995;Elbasiouny et al 2006;Grande et al 2007); however, see (Moritz et al 2007). Due to the speed of mAHP generation following an action potential, the mAHP-causing N-type calcium and N-type calcium activated potassium currents were confined to the soma (also see (Booth et al 1997)).…”