Simulation of Ca2+ Persistent Inward Currents in Spinal Motoneurones: Mode of Activation and Integration of Synaptic Inputs.
From: Department of Biomedical Engineering, University of Alberta, Edmonton, Canada.
The Journal of physiology
- Publish Date: Jan 2006
- ISSN: 0022-3751
- Volume: 570
- Issue: Pt 2
- Pages: 355-74
- Medium: Print
- Language: English
- Citation (JAMA): Elbasiouny Sherif M, Bennett David J, Mushahwar Vivian K, et al. Simulation of Ca2+ Persistent Inward Currents in Spinal Motoneurones: Mode of Activation and Integration of Synaptic Inputs.. J. Physiol. (Lond.) Jan 2006;570:355-74
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.
Mesh Headings (Keywords): Animals, Calcium, Calcium Channels, Cats, Computer Simulation, Dendrites, Membrane Potentials, Models, Neurological, Motor Neurons, Patch-Clamp Techniques, Rats, Spinal Nerves, Synapses, Synaptic Transmission
Check for Full Text / PubMed Unique Identifier (PMID): 16308349
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