PMC

A slowly inactivating outward current in the axon is blocked by 4-AP and α-DTX. (A) Axonal (150 μm from soma) voltage steps activates a slowly inactivating outward current. (B) The slowly inactivating current is blocked by 4-AP (40 μM). (C) Subtraction reveals the 4-AP outward current to be rapidly activating, slowly inactivating, and containing a persistent component. (D) Axonal (110 μm) voltage steps in another cell. (E) α-DTX (100 nM) blocks the slowly inactivating current. (F) Subtraction reveals that α-DTX has effects similar to 4-AP.

A slowly inactivating, 4-AP-sensitive, outward current is prominent in the axon but not the soma. (A) Voltage clamp steps from −85 to −25 mV applied to the soma results in the activation of outward currents, a component of which is blocked by α-DTX. (B) Axonal (120 μm from the soma) voltage clamp steps activate the typical slowly inactivating outward current that is blocked by α-DTX. (C) Plot of the voltage dependence and peak amplitude (as measured at the point illustrated by the arrows) of the α-DTX blocked outward currents, including the noninactivating component.

An α-dendrotoxin-sensitive current controls cortical axonal excitability. (A) Simultaneous somatic and axonal recording. The intraaxonal injection of current pulses results in only single spikes in both the axon and the soma, followed by a slow ramping depolarization of the axon. (B) After bath application of α-dendrotoxin (100 nM; α-DTX) axonal spike threshold is lower, trains of spikes are initiated with moderate amplitude current pulses, the slow depolarizing ramp of the axonal membrane potential in response to depolarization was blocked, and larger intraaxonal current pulses initiated “spikelets” that were not evident in the somatic recording. (C) The application of α-DTX strongly increased axonal spike duration but not in the soma (first spike to each pulse shown). (D) Expansion of two normal spikes and several “spikelets” (in α-DTX). Axon recorded at 110 μm (P20 rat prefrontal cortex).

A 4-AP sensitive current controls slow changes in axonal spike duration. (A) Somatic depolarization rapidly, but only mildly, increases spike duration in the soma (n = 9; single cell traces are shown on right). (B) The somatic depolarization (from an average of −65 to −52 mV) also rapidly depolarizes the axon (top trace; example from one trial in one cell) and slowly increases axonal spike duration over 10s of seconds. (C) Bath application of 4-AP (40 μM) results in a small increase in somatic spike duration. Dashed trace (control) is a spike obtained at hyperpolarized levels before application of 4-AP. (D) The 4-AP increases axonal spike duration and blocks the time-dependent changes with membrane potential. The data presented on the left in A–D are the average of nine cells from ferret PFC. The raw data presented on the right are from one paired somatic-axonal recording (100 μm).

Properties of the slowly inactivating axonal outward current. (A) Axonal voltage steps from a holding potential of −95 mV. (B) Hyperpolarizing steps from a holding potential of −5 mV. (C) Construction of activation and inactivation curves for the slowly inactivating component (n = 9; average recording distance: 99±37 μm). (D) Removal of inactivation after steps to −60, −80, and −100 mV for varying lengths of time (axonal recording 300 μm from the soma). (E) Time course of normalized removal of inactivation data (n = 8; normalized to the tail current after a 5-sec step to −130 mV). Two time courses of removal of inactivation are found, with average time constants of 6.7 and 0.26 sec (average axonal recording distance: 224 ±55 μm). (F) The time constant of the fast component becomes slower with depolarization. (G) The contributions of the faster (first) and slower (second) components varied with voltage.