Shaker-related voltage-gated potassium channels Kv1 in human hippocampus.

Abstract

In this study, we investigated the tissue expression levels, alpha subunit composition and distribution of Shaker-related voltage-dependent potassium Kv1 channels in human hippocampus by combining western blotting experiments, toxin autoradiography, in vivo radioligand binding studies, immunoprecipitation and immunohistochemistry. Tissue expression of Kv1.1 and Kv1.2 α-subunits in human post-mortem brain tissue was confirmed in immunoblot analysis using a panel of specific monoclonal and polyclonal antibodies. Immunoprecipitation experiments using toxin-prelabeled Kv1 channels revealed that all toxin-sensitive Kv1 channels in human hippocampus contained either a Kv1.1 or Kv1.2 α-subunit with the majority being composed of Kv1.1/Kv1.2 heterotetramers. Receptor autoradiography suggested Kv1.1/Kv1.2 channel expression in the molecular layer of dentate gyrus. In accordance, immunohistochemical experiments also observed Kv1.1 and Kv1.2 α-subunits in the molecular layer of the dentate gyrus, in addition to the CA3 stratum lucidum and the CA1 stratum oriens. These findings indicate expression in axons and terminals of hippocampal pathways, namely the perforant path, the mossy fiber pathway and the Schaffer collaterals. Herein we present the first direct demonstration that Kv1.1 and Kv1.2 channel proteins are targeted to distinct compartments of the human hippocampal formation and that this expression pattern largely reflects their distribution profile in murine brain.