Differential Control of Axonal and Somatic Resting Potential by Voltage-Dependent Conductances in Cortical Layer 5 Pyramidal Neurons.

Voltage-dependent conductances not only drive action potentials but also help regulate neuronal resting potential. We found differential regulation of resting potential in the proximal axon of layer 5 pyramidal neurons compared to the soma. Axonal resting potential was more negative than the soma, reflecting differential control by multiple voltage-dependent channels, including sodium channels, Cav3 channels, Kv7 channels, and HCN channels. Kv7 current is highly localized to the axon and HCN current to the soma and dendrite. Because of impedance asymmetry between the soma and axon, axonal Kv7 current has little effect on somatic resting potential, while somatodendritic HCN current strongly influences the proximal axon. In fact, depolarizing somatodendritic HCN current is critical for resting activation of all the other voltage-dependent conductances, including Kv7 in the axon. These experiments reveal complex interactions among voltage-dependent conductances to control region-specific resting potential, with somatodendritic HCN channels playing a critical enabling role.