The role of axonal Kv1 channels in CA3 pyramidal cell excitability

Axonal ion channels control spike initiation and propagation along the axon and determine action potential waveform. We show here that functional suppression of axonal Kv1 channels with local puff of dendrotoxin (DTx), laser or mechanical axotomy significantly increased excitability measured in the cell body. Importantly, the functional effect of DTx puffing or axotomy was not limited to the axon initial segment but was also seen on axon collaterals. In contrast, no effects were observed when DTx was puffed on single apical dendrites or after single dendrotomy. A simple model with Kv1 located in the axon reproduced the experimental observations and showed that the distance at which the effects of axon collateral cuts are seen depends on the axon space constant. In conclusion, Kv1 channels located in the axon proper greatly participate in intrinsic excitability of CA3 pyramidal neurons. This finding stresses the importance of the axonal compartment in the regulation of intrinsic neuronal excitability

Somatic modulation of ectopic action potential initiation in distal axons

International audienceClassically, action potentials are initiated at the axon initial segment (AIS) when the summed depolarizing events arising from the dendrites exceed a threshold value. Then, action potentials propagate along the axon before reaching presynapticterminals where they cause local calcium influx and transmitter release. According to this scheme, the AIS is a major player since all propagated excitation is precisely initiated at this hot spot endowed with a high concentration of sodium channels

Neural excitability increases with axonal resistance between soma and axon initial segment

International audienceThe position of the axon initial segment (AIS) is thought to play a critical role in neuronal excitability. Previous experimental studies have found that a distal shift in AIS position correlates with a reduction in excitability. Yet theoretical work has suggested the opposite, because of increased electrical isolation. A distal shift in AIS position corresponds to an elevation of axial resistance R a . We therefore examined how changes in R a at the axon hillock impact the voltage threshold (V th ) of the somatic action potential in L5 pyramidal neurons. Increasing R a by mechanically pinching the axon between the soma and the AIS was found to lower V th by ∼6 mV. Conversely, decreasing R a by substituting internal ions with higher mobility elevated V th . All R a -dependent changes in V th could be reproduced in a Hodgkin–Huxley compartmental model. We conclude that in L5 pyramidal neurons, excitability increases with axial resistance and therefore with a distal shift of the AIS

The role of axonal Kv1 channels in CA3 pyramidal cell excitability

International audienceAxonal ion channels control spike initiation and propagation along the axon and determine action potential waveform. We show here that functional suppression of axonal Kv1 channels with local puff of dendrotoxin (DTx), laser or mechanical axotomy significantly increased excitability measured in the cell body. Importantly, the functional effect of DTx puffing or axotomy was not limited to the axon initial segment but was also seen on axon collaterals. In contrast, no effects were observed when DTx was puffed on single apical dendrites or after single dendrotomy. A simple model with Kv1 located in the axon reproduced the experimental observations and showed that the distance at which the effects of axon collateral cuts are seen depends on the axon space constant. In conclusion, Kv1 channels located in the axon proper greatly participate in intrinsic excitability of CA3 pyramidal neurons. This finding stresses the importance of the axonal compartment in the regulation of intrinsic neuronal excitability