RT Journal Article SR Electronic T1 Functional specification of CCK+ interneurons by alternative isoforms of Kv4.3 auxiliary subunits JF bioRxiv FD Cold Spring Harbor Laboratory SP 683755 DO 10.1101/683755 A1 Oláh, Viktor János A1 Lukacsovich, David A1 Winterer, Jochen A1 Lőrincz, Andrea A1 Nusser, Zoltan A1 Földy, Csaba A1 Szabadics, János YR 2019 UL http://biorxiv.org/content/early/2019/06/27/683755.abstract AB CCK-expressing interneurons (CCK+INs) are crucial for controlling hippocampal activity. We found two firing phenotypes of CCK+INs in rat CA3 area; either possessing a previously undetected membrane potential-dependent firing or regular firing phenotype, due to different low-voltage-activated potassium currents. These different excitability properties destine the two types for distinct functions, because the former is essentially silenced during realistic 8-15 Hz oscillations. The general excitability, morphology and gene-profiles of the two types were surprisingly similar. Even the expression of Kv4.3 channels were comparable, despite evidences showing that Kv4.3-mediated currents underlie the distinct firing properties. Instead, the firing phenotypes were correlated with the presence of distinct isoforms of Kv4 auxiliary subunits (KChIP1 vs. KChIP4e and DPP6S). Our results reveal the underlying mechanisms of two previously unknown types of CCK+INs and demonstrate that alternative splicing of few genes, which may be viewed as a minor event in the cells’ whole transcriptome, can underlie distinct cell-type identity.