The first of the distinctive family of two transmembrane domain inward rectifier K+ channels to be cloned was ROMK11, now known as Kir1.1 (see2). The name of these channels is based on their location; renal outer medullary K+ channel (ROMK). These channels are involved in electrolyte processing in the kidney and serve to regulate K+ recycling in the thick ascending loop of Henle and mediate K+ secretion in the distal nephron (see3). In addition, the channel is expressed in brain mainly in the cortex and hippocampus4. There are six known splice variants, products of the same gene designated Kir1.1a-f (according to the nomenclature suggested in2). Many of the splice variants are differentially expressed along the nephron in the kidney, probably contributing locally to electrolyte processing. One variant, Kir1.1f is ubiquitously expressed in many tissues including brain, heart and skeletal muscle5. Two other families of Kir channels, Kir4 and Kir7, are structurally related to Kir1.1 proteins and were initially marked as members of the same family. These are Kir4.1, Kir4.2 and Kir7.1, which are widely expressed and have different biophysical properties compared to Kir1.1 channels6,7.
The activity of ROMK channels was shown to be modulated by many cytosolic factors including protons, ATP and phosphorylation. These channels also interact with the cystic fibrosis transmembrane regulator (CFTR)8 and with the sulfonylurea receptor (SUR2B)9, which are both regarded as auxiliary subunits for K+ (and other) channels.
Like all inward rectifier K+ channels, external Ba2+ also blocks ROMK channels. The bee venom peptide, Tertiapin (#STT-250), which is also a general Kir blocker, effectively blocks ROMK channels10, and δ-Dendrotoxin (#D-380), which is a blocker of some KV channels, blocks also ROMK1 channels with Kd of 150 nM11. However, a scorpion toxin, Lq2, specifically and potently inhibits ROMK1 channels12. The physiological importance of these channels is stressed by the finding that mutations in this gene lead to Bartter’s syndrome, an autosomal recessive disease affecting the kidney (see3,13).
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