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

Abstract

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.

Theoretical relation between axon initial segment geometry and excitability

“…Note that the resting potential is different 161 at the two sites; we will come back to this issue in a later section. As noted by Hu and Bean (2018), the 162 axonal input resistance increases with distance of the injection site. When measured 300 µs after the 163 start of the pulse, the axonal input resistance increases steeply with distance, while the soma barely 164 responds ( Fig.…”

“…Is this effect likely to be substantial in neurons? Empirically, Hu & Bean (2018) found that in layer 5 515 pyramidal cells, the AIS (more precisely, the axonal bleb) is about 3 mV hyperpolarized relative to the 516 soma. This suggests that the contribution of this effect to threshold variations should be small.…”

Axonal Na+ channels detect and transmit levels of input synchrony in local brain circuits

“…Second, the presence of neuromodulators such as acetylcholine would significantly promote ISF. In fact, acetylcholine specifically depolarizes axon membrane potential by blocking Kv7 channels 38 and reduces sodium current 39 , which should increase ISF (see TTX experiment, Suppl. Fig 6).…”

KCNQ channels enable reliable presynaptic spiking and synaptic transmission at high-frequency

“…KCNQ channels are well-suited to this role. At rest, a small proportion of KCNQ channels are activated (Wladyka and Kunze, 2006; Huang and Trussell, 2011; Hu and Bean, 2018), contributing to establishing the resting potential and the baseline responsiveness of soma, axon, and synapse. However, we show here that during repetitive activity, gradual depolarization of the membrane reduces availability of Na + channels, and to a lesser extent Kv1 channels.…”