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Chunk #1 — Introduction

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Developmental regulation of G protein-gated inwardly-rectifying K+ (GIRK/Kir3) channel subunits in the brain.
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Four different genes encode GIRK channel subunits in mammals (GIRK1–4), which combine to form functional homotetrameric or heterotetrameric channels (Krapivinsky et al., 1995; Lesage et al., 1995). Three channel subunits (GIRK1–GIRK3) exhibit broad and partly overlapping distributions in the central nervous system, whereas GIRK4 expression is limited to a small number of neuron populations (Karschin et al., 1996; Perry et al., 2008; Wickman et al., 2000). The overlapping distribution of neuronal GIRK channels suggests the potential for considerable molecular diversity (Karschin et al., 1996). In the brain, GIRK2 contributes to the formation of most GIRK channels (reviewed by Luján et al., 2009; Lüscher & Slesinger, 2010), determining their assembly and surface localization (Inanobe et al., 1999). The GIRK1 subunit assembles with GIRK2 (Koyrakh et al., 2005; Liao et al., 1996; Marker et al., 2004), and the similar electrophysiological profiles of neurons from GIRK1−/− and GIRK2−/− mice support this notion (Koyrakh et al., 2005; Marker et al., 2006). Recent evidence suggests that many GIRK channel subtypes exist in the brain in a cell type- and subcellular compartment-dependent manner (Aguado et al.,