Ca2+-activated KCa3.1 potassium channels contribute to the slow afterhyperpolarization in L5 neocortical pyramidal neurons

Autor: Pavel M. Balaban, M. V. Roshchin, V. N. Ierusalimsky, E. S. Nikitin
Rok vydání: 2020
Předmět:
Zdroj: Scientific Reports
Scientific Reports, Vol 10, Iss 1, Pp 1-10 (2020)
ISSN: 2045-2322
Popis: Layer 5 neocortical pyramidal neurons are known to display slow Ca2+-dependent afterhyperpolarization (sAHP) after bursts of spikes, which is similar to the sAHP in CA1 hippocampal cells. However, the mechanisms of sAHP in the neocortex remain poorly understood. Here, we identified the Ca2+-gated potassium KCa3.1 channels as contributors to sAHP in ER81-positive neocortical pyramidal neurons. Moreover, our experiments strongly suggest that the relationship between sAHP and KCa3.1 channels in a feedback mechanism underlies the adaptation of the spiking frequency of layer 5 pyramidal neurons. We demonstrated the relationship between KCa3.1 channels and sAHP using several parallel methods: electrophysiology, pharmacology, immunohistochemistry, and photoactivatable probes. Our experiments demonstrated that ER81 immunofluorescence in layer 5 co-localized with KCa3.1 immunofluorescence in the soma. Targeted Ca2+ uncaging confirmed two major features of KCa3.1 channels: preferential somatodendritic localization and Ca2+-driven gating. In addition, both the sAHP and the slow Ca2+-induced hyperpolarizing current were sensitive to TRAM-34, a selective blocker of KCa3.1 channels.
Databáze: OpenAIRE