Simulation of Ca+2 Persistent Inward Currents in Spinal Motoneurons: Mode of Activation and Integration of Synaptic Inputs

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The goal of this study was to investigate the nature of activation of the dendritic calcium persistent inward current (Ca2+ PIC) and its contribution to the enhancement and summation of synaptic inputs in spinal motoneurones. A compartmental cable model of a catα-motoneurone was developed comprising the realistic dendritic distribution of Ia-afferent synapses and low-voltage-activated L-type calcium (Cav1.3) channels distributed over the dendrites in a manner that was previously shown to match a wide set of experimental measurements. The level of synaptic activation was systematically increased and the resulting firing rate, somatic and dendritic membrane potentials, dendritic Cav1.3 channel conductance, and dendritic Ca2+ PIC were measured. Our simulation results suggest that during cell firing the dendritic Ca2+ PIC is not activated in an all-or-none manner. Instead, it is initially activated in a graded manner with increasing synaptic input until it reaches its full activation level, after which additional increases in synaptic input result in minimal changes in the Ca2+ PIC (PIC saturated). The range of graded activation of Ca2+ PICoccurs when the cell is recruited and causes a steep increase in the firing frequency as the synaptic current is increased, coinciding with the secondary range of the synaptic frequency–current (F–I)relationship.Once theCa2+ PICissaturated the slope of theF–I relationship is reduced, corresponding to the tertiary range of firing.When the post-spike after-hyperpolarization (AHP) is blocked, either directly by blocking the calcium-activated potassium channels, or indirectly by blocking the sodium spikes, the PIC is activated in an all-or-none manner with increasing synaptic input. Thus, the AHP serves to limit the depolarization of the cell during firing and enables graded, rather than all-or-none, activation of the Ca2+ PIC. The graded activation of the Ca2+ PIC with increasing synaptic input results in a graded (linear) enhancement and linear summation of synaptic inputs. In contrast, the saturated Ca2+ PIC enhances synaptic inputs by a constant amount (constant current), and leads to less-than linear summation of multiple synaptic inputs. These model predictions improve our understanding of the mode of activation of the dendritic Ca2+ PIC and its role in the enhancement and integration of synaptic inputs.


This article was ranked by the Journal of Physiology among the Top 10 Research Papers published in that issue of the journal based on the number of electronic access and downloads.



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