Computational Estimation of the Distribution of L-type Ca2+ Channels in Motoneurons Based on Variable Threshold of Activation of Persistent Inward Currents

Canadian Institute for Health Research Group in Sensory-Motor Systems, Department of Physiology, Centre for Neuroscience Studies, Queen’s University, Kingston, Canada Submitted 22 June 2005; accepted in final form 17 September 2005 In the presence of neuromodulators such as serotonin and noradrenaline, motoneurons exhibit persistent inward currents (PICs) that serve to amplify synaptic inputs. A major component of these PICs is mediated by L-type Ca 2+ channels. Estimates based on electrophysiological studies indicate that these channels are located on the dendrites, but immunohistochemical studies of their precise distribution have yielded different results. Our goal was to determine the distribution of these channels using computational methods. A theoretical analysis of the activation of PICs by a somatic current injection in the absence or presence of synaptic activity suggests that L-type Ca 2+ channels may be segregated to discrete hot spots 25–200 µm long and centered 100–400 µm from the soma in the dendritic tree. Compartmental models based on detailed anatomical measurements of the structure of feline neck motoneurons with L-type Ca 2+ channels incorporated in these regions produced plateau potentials resulting from PIC activation. Furthermore, we replicated the experimental observation that the somatic threshold at which PICs were activated was depolarized by tonic activation of inhibitory synapses and hyperpolarized by tonic activation of excitatory synapses. Models with L-type Ca 2+ channels distributed uniformly were unable to replicate the change in somatic threshold of PIC activation. Therefore we conclude that the set of L-type Ca 2+ channels mediating plateau potentials is restricted to discrete regions in the dendritic tree. Furthermore, this distribution leads to the compartmentalization of the dendritic tree of motoneurons into subunits whose sequential activation lead to the graded amplification of synaptic inputs. Address for reprint requests and other correspondence: P. K. Rose, Dept. of Physiology, Botterell Hall, Queen’s University, Kingston K7L 3N6, Canada (E-mail: ken{at}biomed.queensu.ca )