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. 2019 Aug 19;151(10):1173–1189. doi: 10.1085/jgp.201912457

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© 2019 Bailey et al.

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Figure 3. — BK channel dysfunction by organ and functional system in rodent models. BK channel knockout mice (KCNMA1^−/−) show a wider range of pathophysiology compared with human KCNMA1 patients with LOF mutations. Such findings are consistent with the extensive distribution of BK channels across tissues. Key organ and functional systems disrupted by BK channel dysfunction in mouse models are indicated. BK channel activity was required for several aspects of neurological operations in rodent models, such as regulation of neuronal excitability (Jin et al., 2000; Faber and Sah, 2003; Brenner et al., 2005; Shruti et al., 2008; Sheehan et al., 2009), locomotor function (Meredith et al., 2004; Sausbier et al., 2004; Chen et al., 2010), circadian rhythm (Meredith et al., 2006; Kent and Meredith, 2008; Montgomery et al., 2013; White et al., 2015; Whitt et al., 2016), learning and memory (Typlt et al., 2013b), vision (Henne and Jeserich, 2004; Grimes et al., 2009; Tanimoto et al., 2012), hearing and vestibular reflexes (Pyott et al., 2007; Maison et al., 2013; Rohmann et al., 2015; Pyott and Duncan, 2016; Nelson et al., 2017), and neurovascular coupling (Filosa et al., 2006; Girouard et al., 2010). In addition to neurological roles, rodent models further revealed that BK channels are required for regulation of cardiovascular function (Sausbier et al., 2005; Imlach et al., 2010; Lai et al., 2014; Nagaraj et al., 2016), airway control (Sausbier et al., 2007; Goldklang et al., 2013; Manzanares et al., 2014), urination (Meredith et al., 2004; Thorneloe et al., 2005; Brown et al., 2008; Sprossmann et al., 2009), glucose homeostasis (Houamed et al., 2010; Düfer et al., 2011), renal K⁺ homeostasis (Liu et al., 2007; Rieg et al., 2007), reproductive function (Werner et al., 2005, 2008; Li et al., 2014), ethanol intoxication (Martin et al., 2004; Pietrzykowski et al., 2008), gastrointestinal function (Sausbier et al., 2006a; Sørensen et al., 2008), body weight (Halm et al., 2017), pain (Hayashi et al., 2016), immunity (Essin et al., 2009), bone remodeling (Sausbier et al., 2011; Hei et al., 2016), and salivary secretion (Maruyama et al., 1983; Stummann et al., 2003).