Volume 85, Issue 2, Pages 238-256 (January 2015) Subcellular Localization of K+ Channels in Mammalian Brain Neurons: Remarkable Precision in the Midst of Extraordinary Complexity  James S. Trimmer  Neuron  Volume 85, Issue 2, Pages 238-256 (January 2015) DOI: 10.1016/j.neuron.2014.12.042 Copyright © 2015 Elsevier Inc. Terms and Conditions

Figure 1 Simplified Overview of KCh Subcellular Localization Dendrogram format is derived from that available as an online resource courtesy of Fabrice Duprat (https://www.ipmc.cnrs.fr/∼duprat/ipmc/nomenclature.htm), and is not meant to convey precise evolutionary relationships. Subcellular localization is based on certain brain neuron classes as detailed in text, and is meant as a general simplified overview, and does not universally apply to all species, brain regions, neuron types and developmental stages. Neuron 2015 85, 238-256DOI: (10.1016/j.neuron.2014.12.042) Copyright © 2015 Elsevier Inc. Terms and Conditions

Figure 2 K+ Channel Localization in Hippocampal CA1 Apical Dendrites (A) Cartoon showing localization of KChs in dendritic spines. See text for details. (B) Double LM-IF labeling for Kv4.2 (red) and PSD-95 (green) in rat CA1 showing robust labeling for Kv4.2 in sr versus slm. Scale bar, 100 μm. (C) LM-DAB labeling for Kv4.2 (far left), KChIP2 (middle left), KChIP4 (middle right), and Kv2.1 (far right) in rat CA1. Scale bar, 50 μm. Modified from Rhodes et al. (2004). (D) EM-IG labeling for Kv4.2 (small particles) and PSD-95 (large particles) in a SDS-FRL sample from rat CA1 showing a single excitatory synapse (at, axon terminal; sp, spine). Scale bar, 0.1 μm. From Kerti et al. (2012). Anatomical labels for (B) and (C) are as follows: CA1, so, stratum oriens; sp, stratum pyramidale; sr, stratum radiatum; and slm, stratum lacunosum moleculare. Neuron 2015 85, 238-256DOI: (10.1016/j.neuron.2014.12.042) Copyright © 2015 Elsevier Inc. Terms and Conditions

Figure 3 K+ Channel Localization in Dendrites and Somata (A) LM-IF labeling for Kir3.1 (left) and Kir3.2 (right) in rat hippocampal CA1. From Kirizs et al. (2014). Scale bar, 100 μm. (B) EM-IG labeling for KCa2.2 (large particles, 10 nm) and PSD-95 (small particles, 5 nm) showing extrasynaptic KCa2.2 within a dendritic spine (sp) at an excitatory synapse (at, axon terminal) in a SDS-FRL sample from mouse CA1. Scale bar, 0.2 μm. From Ballesteros-Merino et al. (2012). (C) EM-IG labeling of Kir3.2, GABA-B1 receptors, and PSD-95 in a SDS-FRL sample from rat CA1 showing colocalization of Kir3.2, GABA-B1 receptors in the extrasynaptic membrane of a dendritic spine (s) emerging from a dendrite (Den). Scale bar, 0.2 μm. From Kulik et al. (2006). (D) Double LM-IF labeling for Kv4.2 (red) and Kv2.1 (green) in rat CA1 showing precise compartmentalization of these KChs across different hippocampal strata. Scale bar, 100 μm. (E) Superresolution (SIM) image of a double label LM-IF of Kv2.1 (green) and ryanodine receptor (red) in a mouse striatal medium spiny neuron. Scale bar, 2 μm. From Mandikian et al. (2014). Anatomical labels for (A) and (D) are as in Figure 2. Neuron 2015 85, 238-256DOI: (10.1016/j.neuron.2014.12.042) Copyright © 2015 Elsevier Inc. Terms and Conditions

Figure 4 K+ Channel Localization in the Axon Initial Segment (A) Cartoon showing localization of KChs in the AIS. See text for details. (B) Double LM-IF labeling for Kv1.2 (red) and Nav1.6 (green) in a pyramidal neuron in rat neocortex layer 5 showing distal compartmentalization of Kv1.2. Scale bar, 5 μm. From Lorincz and Nusser (2008a). (C) Double LM-IF labeling for Kv7.2 (green) and AnkG (red) in a field of pyramidal neurons in rat neocortex layer 5 (right panel) and a single neuron (left panel) showing distal compartmentalization of Kv7.2. Scale bars, 10 μm. From Battefeld et al. (2014). (D) Superresolution (SIM) image of double label LM-IF of Kv2.1 (green), and AnkG (red) showing the localization of Kv2.1 in “holes” in the AnkG matrix within the AIS of a rat neocortical pyramidal neuron. Right panel is same image without Kv2.1. Scale bar, 2 μm. From King et al. (2014). (E) Superresolution (SIM) image of triple label LM-IF of Kv2.1 (green), Nav1.6 (red), and AnkG (blue), showing the mosaic of expression of these proteins within the AIS of a rat neocortical pyramidal neuron. Right panel is same image without Kv2.1, showing sites of Kv2.1 labeling are in holes of AnkG and Nav1.6 labeling. Scale bar, 1 μm. (F) Triple label LM-IF of nodal Kv7.2 (red) and AnkG (green), and juxtaparanodal Kv1.2 (blue) in rat brainstem, sample fixed at pH 6.0. Scale bar, 5 μm. (G) Kv1.2 (red) at JPNs and neurofascin-155 (green) at paranodes, in samples from multiple sclerosis patients. Images show labeling of normal-appearing white matter (far left), and two examples of demyelinated white matter in which Kv1.2 labeling is disrupted. Scale bars, 5 μm. From Howell et al. (2006). (H) Cartoon showing overall expression of axonal KChs in domains at/near the node of Ranvier. See text for details. Neuron 2015 85, 238-256DOI: (10.1016/j.neuron.2014.12.042) Copyright © 2015 Elsevier Inc. Terms and Conditions

Figure 5 K+ Channel Localization in Hippocampal Mossy Fibers (A) Cartoon showing localization of KChs at/near presynaptic terminals. See text for details. (B) Double label LM-IF labeling for Kv1.1 (green) and Nav1.2 (red) in mouse hippocampus, showing localization in MFs. Scale bar, 200 μm. (C) EM-DAB labeling for Kv1.4 in stratum lucidum of CA3 in rat. From Cooper et al. (1998). MFE, mossy fiber expansion. MT, microtubules. Scale bars, 0.2 μm. (D) Double LM-IF labeling for KCa1.1 (green) and VGlut1 (red) in mouse hippocampus, showing KCa1.1 localization in MFs. Scale bar, 200 μm. Neuron 2015 85, 238-256DOI: (10.1016/j.neuron.2014.12.042) Copyright © 2015 Elsevier Inc. Terms and Conditions