Activity-dependent regulation of axon initial segment potassium channels

Abstract

Voltage-gated potassium channels critically impact action potential firing in our nervous system. Many of these channels like Kv1.1, Kv2.1, and Kv7.2 are located at the axon initial segment (AIS). Because of its high complexity, the segment has been linked to many neurological disorders like ataxia and multiple types of epilepsy. In recent years, it was revealed that the AIS is susceptible to relocation as a feedback mechanism to varying neuronal activity levels, referred to as AIS plasticity. However, It is currently unknown whether AIS potassium channels also experience relocation in this process. In this project, we performed confocal and stimulated emission depletion (STED) imaging on rat hippocampal neurons to uncover the effect of activity manipulation on AIS Kv1.1, Kv2.1, and Kv7.2. All examined potassium channels experienced a decreased expression after 48 hours of activity deprivation, indicating neurons limit their hyperpolarizing capability. Kv2.1 was linked to a biphasic response, resulting from an increased cluster intensity, followed by an overall decreased number of clusters after prolonged activity deprivation. It was hypothesized that internal mechanisms try to traffic diffuse channels to the clusters where they become nonconducting, rapidly limiting their action potential inhibition. These results indicate that potassium channels are regulated by neuronal activity and subject to the processes of AIS plasticity. Therefore, they proved to be compelling candidates for future research.