title: Simulation of Ca2+ persistent inward currents in spinal motoneurones: mode of activation and integration of synaptic inputs.
abstract: The goal of this study was to investigate the nature of activation of the dendritic calcium persistent inward current (Ca(2+) PIC) and its contribution to the enhancement and summation of synaptic inputs in spinal motoneurones. A compartmental cable model of a cat alpha-motoneurone was developed comprising the realistic dendritic distribution of Ia-afferent synapses and low-voltage-activated L-type calcium (Ca(v)1.3) 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 Ca(v)1.3 channel conductance, and dendritic Ca(2+) PIC were measured. Our simulation results suggest that during cell firing the dendritic Ca(2+) 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 Ca(2+) PIC (PIC saturated). The range of graded activation of Ca(2+) PIC occurs 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 the Ca(2+) PIC is saturated the slope of the F-I relationship is reduced, corresponding to the tertiary range of firing. When the post-spike afterhyperpolarization (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 Ca(2+) PIC. The graded activation of the Ca(2+) PIC with increasing synaptic input results in a graded (linear) enhancement and linear summation of synaptic inputs. In contrast, the saturated Ca(2+) 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 Ca(2+) PIC and its role in the enhancement and integration of synaptic inputs.
authors.affiliation: Department of Biomedical Engineering, University of Alberta, Edmonton, Canada.
authors.forename: Sherif M
authors.initials: SM
authors.lastname: Elbasiouny
authors.forename: David J
authors.initials: DJ
authors.lastname: Bennett
authors.forename: Vivian K
authors.initials: VK
authors.lastname: Mushahwar
mesh_terms: D000818:Animals; D002118:Calcium / Q000502:physiology*; D015220:Calcium Channels / Q000502:physiology; D002415:Cats; D003198:Computer Simulation; D003712:Dendrites / Q000502:physiology; D008564:Membrane Potentials / Q000502:physiology; D008959:Models, Neurological; D009046:Motor Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques; D051381:Rats; D013127:Spinal Nerves / Q000502:physiology*; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D015220:Calcium Channels; D002118:Calcium