Moody Laboratory: Ion channel development in mouse cortical neurons |
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Ion channels and electrical coupling in the mouse ventricular zone
Many of the neurons of the neocortex are generated during embryonic development from a stem cell population in the ventricular zone (VZ). We studied the electrical properties of these VZ cells in mouse using whole-cell voltage clamp methods. Injection of the dye Neurobiotin, which crosses gap junctions, typically stains a large coupled cluster of VZ cells, including those of radial glial morphology (see Figure at left). Blocking gap junctions with octanol blocks this dye coupling. Experiments in rat VZ have shown that this extensive dye coupling is accompanied by strong electrical coupling. Our experiments in mouse show that although dye coupling in mouse VZ is similar to that in rat, electrical coupling in mouse is quite weak. This allowed us to voltage clamp mouse VZ cells accurately, without resorting to uncoupling methods. You can read about this work in: Picken-Bahrey, HP and Moody, WJ. Cerebral Cortex 13, 239-251 (2003) Ion channel development in cortical plate neurons
We have also studied the development of Na and K currents in cortical plate neurons through the embryonic and early postnatal periods. As shown the graph to the left, Na current density in cortical plate neurons increases about 4-fold between E14 and P2. Delayed K current density, in contrast, does not change during this period. This means that when a VZ stem cell exits the cell cycle, it beging to express functional Na currents, which then increase steady throughout early development. Delayed K currents, on the other hand, are present in VZ stem cells and do not change in density after cell cycle exit, or during migration and early differentiation in the cortical plate. The increasing ratio of inward Na to outward K currents would be exprected to increase neuronal excitability during this time. This is confirmed both by current clamp recordings showing marked increases in excitability and repetitive firing ability between E14 and P10. You can read about this work in: Picken-Bahrey, HP and Moody, WJ. J. Neurophysiol. 89, 1761-1773 (2003). |
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Last modified:Oct. 2010 |