Inactivating axonal Kv1 channels and long length constant of the axonal cable are the key mechanisms underlying axonal AP modulation.

<p>(A) Top, K⁺ current evoked in outside-out patches from the axon (434 µm) of CA1 pyramidal neuron by 200-ms pulses to 50 mV in the absence (Black trace, I_Control) and presence (Gray trace, I_{100 nM α-DTX}) of 100 nM α-DTX. Middle, the blue trace represents the α-DTX-sensitive current component obtained by digital subtraction. Bottom, bar plot of the average time constant of inactivation (n = 10). (B) Summary bar graph showing the effect of 100 nM α-DTX in axonal patches (left, P<0.001, n = 13) and somatic patches (right, P>0.1, n = 6). Bars indicate mean ± SEM; circles denote individual experiments. Data points for the same experimental conditions are connected by lines. (C) Recovery of α-DTX-sensitive K⁺ channel from inactivation. Stimulation protocol and example traces of recovery from inactivation, as probed with a double-pulse protocol (100-ms prepulse to –120 mV, 150-ms conditioning pulses and 30-ms test pulses to +50 mV, separated by a recovery interval of variable duration at –120 mV). The holding potential before and after the pulse protocol was –90 mV. Axonal patch is 388 µm from the soma. (D) Summary plot of the amplitude of the peak current evoked by the test pulse, divided by that evoked by the conditioning pulse, plotted against interpulse interval. Data points represent means from 5 patches. Red curves represent double-exponential fit to the data points. (E, F) Gating properties of α-DTX-sensitive axonal K⁺ channels. Stimulation protocol and traces of activation and steady-state inactivation of α-DTX-sensitive K⁺ channels in CA1 pyramidal neuron axons. (E) To probe steady-state activation, a 100-ms prepulse to –120 mV was followed by a 200-ms test pulse to various potentials (–120 to 50 mV). (F) To test steady-state inactivation, a 5-s prepulse to various potentials (–120 to 0 mV) was followed by a 200-ms test pulse to 50 mV. Axonal patch is 423 µm from the soma. (G) Activation (blue circles) and steady-state inactivation (black squares) curves. Conductance values were normalized to the maximal value. Data points represent means from 8 patches for activation curve and 6 patches for steady-state inactivation. Blue curves represent Boltzmann functions fit to the data points. For the activation curve (blue line), the midpoint potential was –12 mV and the sloe factor 26.4 mV. For the inactivation curve (black line), the midpoint potential was –64 mV and the slope factor 15.2 mV. (H) Length constant of the CA1 pyramidal neuron axons. Plot of axonal to somatic voltage deflection during hyperpolarizing current pulses (1 s, –30 pA) applied at the soma, plotted against distance. Each data point represents a simultaneous axon–soma recording. Red line represents a fit of data points with an exponential function, resulting in a mean length constant of 712 µm. Note that the long length constant results in particularly efficient propagation of subthreshold membrane potential changes from the soma to the axon. (Inset) voltage changes recorded in the soma (black) and the axon (blue) during hyperpolarizing current pulses applied at the soma. Axonal recording site is 705 µm from the soma. Traces shown represent average of 20 (A, black trace), 22 (A, gray trace), 2 (C), 3 (E), and 2 (F) single sweeps. Transient inward Na⁺ currents at the beginning of the pulse are truncated. Error bars, SEM.