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

Canadian Institute for Health Research Group in Sensory-Motor Systems, Department of Physiology, Centre for Neuroscience Studies, Queen's University, Kingston, Ontario, Canada Submitted 12 January 2007; accepted in final form 9 April 2007 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. Address for reprint requests and other correspondence: G. Grande, Dept. of Physiology, 4th Floor Botterell Hall, Queen's Univ., Kingston, Ontario K7L 3N6, Canada (E-mail: john{at}biomed.queensu.ca )