Although action potentials propagate along axons in an all-or-none manner, subthreshold membrane potential fluctuations at the soma affect neurotransmitter release from synaptic boutons. An important mechanism underlying analog-digital modulation is depolarizationmediated inactivation of presynaptic Kv1-family potassium channels, leading to action potential broadening and increased calcium influx. Previous studies have relied heavily on recordings from blebs formed after axon transection, which may exaggerate the passive propagation of somatic depolarization. We recorded instead from small boutons supplied by intact axons identified with scanning ion conductance microscopy in primary hippocampal cultures and asked how distinct potassium channels interact in determining the basal spike width and its modulation by subthreshold somatic depolarization. Pharmacological or genetic deletion of Kv1.1 broadened presynaptic spikes without preventing further prolongation by brief depolarizing somatic prepulses. A heterozygous mouse model of episodic ataxia type 1 harboring a dominant Kv1.1 mutation had a similar broadening effect on basal spike shape as deletion of Kv1.1; however, spike modulation by somatic prepulses was abolished. These results argue that the Kv1.1 subunit is not necessary for subthreshold modulation of spike width. However, a disease-associated mutant subunit prevents the interplay of analog and digital transmission, possibly by disrupting the normal stoichiometry of presynaptic potassium channels.channelopathy | synaptic transmission | potassium channel A lthough action potentials are generated at the axon initial segment in an all-or-none manner, synaptic transmission can be modulated by electrotonic propagation of subthreshold membrane depolarization from the soma (1-6). Inactivation of axonal Kv1-family channels contributes to "analog" signaling by broadening presynaptic action potentials (6-9). Investigations of presynaptic spike shape in small presynaptic boutons have relied heavily on extrapolation from recordings in blebs that form after axons have been transected (2,6,8,9). A potential pitfall of this method is that the ion channels present in blebs may not be representative of the normal complement of channels at an unperturbed bouton. A further difficulty is that the attenuation of voltage with distance from the soma is likely to be smaller than when recording from an intact axon. Indeed, classical cable theory predicts that steady-state somatic voltage should decrease by ∼63% at one length constant if the axon is represented by an infinite cable, but only by ∼35% if it is sealed at the same point (10). The discrepancy increases as the axon is made shorter: if the axon is cut at half a length constant, the attenuation of steady-state voltage at its termination is only ∼29% of that predicted for an infinite cable. Given that the length constant of unmyelinated axons in the CNS has been estimated in the range of 400-600 μm (1-3, 9, 11), this implies that the modulation of action potential shape...