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Spatial mismatch between the Na+ flux and spike initiation in axon initial segment
Gytis Baranauskas1, Yaron David, Ilya A Fleidervish
1Department of Physiology and Cell Biology, Faculty of Health Sciences and Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer Sheva 84105, Israel.
Action potentials initiate in the axon initial segment (AIS) due to cable properties, not just sodium channel density. This finding impacts understanding neuronal excitability and plasticity.
Area of Science:
- Neuroscience
- Computational Neuroscience
Background:
- Action potentials (APs) are fundamental to neuronal communication.
- The axon initial segment (AIS) is the primary site of AP initiation in cortical pyramidal cells.
- High sodium (Na+) channel density in the AIS is traditionally thought to drive AP initiation.
Purpose of the Study:
- To investigate the precise relationship between Na+ channel density and the spatiotemporal pattern of AP initiation.
- To determine the factors governing the exact location of AP initiation within the AIS.
Main Methods:
- Simultaneous recording of Na+ flux and action currents along the proximal axonal length.
- Computational modeling of AP initiation dynamics.
- Analysis of current source-load ratios and capacitive loading.
Main Results:
- Functional Na+ channel density is significantly lower at the AP trigger zone compared to the middle of the AIS.
- A mismatch exists between AP threshold and Na+ channel density, explained by somatodendritic capacitive load.
- Optimal conditions for AP initiation are found in the distal AIS, near myelin.
Conclusions:
- Cable properties of the axon and somatodendritic compartment critically influence AP initiation site.
- Neuronal excitability is highly sensitive to local changes in AIS Na+ channel density.
- The distal AIS, not the region of highest Na+ channel density, is the primary site for AP initiation.
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