Voltage-gated potassium channels ensure action potential shape fidelity in distal axons

The initiation and propagation of the action potential (AP) along an axon allows neurons to convey information rapidly and across distant sites. Although AP properties have typically been characterised at the soma and proximal axon, the propagation of APs towards distal axonal domains of mammalian neurons remains limited. We used Genetically Encoded Voltage Indicators (GEVIs) to image APs simultaneously at different locations along the long axons of dissociated hippocampal neurons with sub-millisecond temporal resolution. We found that APs became sharper and showed remarkable fidelity as they traveled towards distal axons, even during a high frequency train. Blocking voltage-gated potassium channels (Kv) with 4-AP resulted in an increase in AP width in all compartments, which was stronger at distal locations and exacerbated during AP trains. We conclude that the higher levels of Kv channel activity in distal axons serves to sustain AP fidelity, conveying a reliable digital signal to presynaptic boutons.

The Yin and Yang of BK Channels in Epilepsy

Background & Objective: The large conductance calcium-activated potassium (BK) channel, extensively distributed in the central nervous system (CNS), is considered as a vital player in the pathogenesis of epilepsy, with evidence implicating derangement of K+ as well as regulating action potential shape and duration. However, unlike other channels implicated in epilepsy whose function in neurons could clearly be labeled “excitatory” or “inhibitory”, the unique physiological behavior of the BK channel allows it to both augment and decrease the excitability of neurons. Thus, the role of BK in epilepsy is controversial so far, and a growing area of intense investigation. Conclusion: Here, this review aims to highlight recent discoveries on the dichotomous role of BK channels in epilepsy, focusing on relevant BK-dependent pro- as well as antiepileptic pathways, and discuss the potential of BK specific modulators for the treatment of epilepsy.