1.A.2.1.1
ATP-activated inward rectifier K⁺ channel, IRK1 (also called ROMK or KIR1.1) (regulated by Sur1, allowing ATP sensitivity; also activated by phosphatidylinositol 4,5-bisphosphate (PIP) with affinity to PIP controlled by protein kinase A phosphorylation (which increases affinity for PIP) and protein kinase C phosphorylation (which decreases affinity for PIP (Zeng et al., 2003). The mechanism of voltage sensitivity of IRK1 inward-rectifier K⁺ channel block by the polyamine, spermine, has been proposed (Shin and Lu 2005). A putative pH sensor has been identified (Rapedius et al. 2006). Closure of the Kir1.1 pH gate results from steric occlusion of the permeation path by the convergence of four leucines (or phenylalanines) at the cytoplasmic apex of the inner transmembrane helices. In the open state, K⁺ crosses the pH gate together with its hydration shell (Sackin et al. 2005). Alternariol (AOH), the most important mycotoxin produced by Alternaria species, which are the most common mycoflora infecting small grain cereals worldwide, causes loss of cell viability by inducing apoptosis. AOH-induced apoptosis through a mitochondria-dependent pathway is characterized by p53 activation, an opening of the mitochondrial permeability transition pore (PTP), loss of mitochondrial transmembrane potential (ΔΨm), a downstream generation of O₂^- and caspase 9 and 3 activation (Bensassi et al., 2012). Pharmacological inhibition of renal ROMK causes diuresis and natriuresis in the absence of kaliuresis (Garcia et al. 2013). Cholesterol binding sites in KIR channels have been identified (Rosenhouse-Dantsker 2019). The ubiquitously expressed family of inward rectifier potassium (KIR) channels, encoded by KCNJ genes, is primarily involved in cell excitability and potassium homeostasis. Disease-associated mutations in KIR proteins have been linked to aberrant inward rectifier channel trafficking (Zangerl-Plessl et al. 2019). Interfacial binding Ssites for cholesterol on Kir, Kv, K2P, and related potassium channels have been identified (Lee 2020). Decreasing pH(in) increases the sensitivity of ROMK2 channels to K⁺(out) by altering the properties of the selectivity filter (Dahlmann et al. 2004).