Kir1.1 (ROMK1) was the first member of the family of inward rectifying K+ channels to be cloned.1 The family includes 15 members that are structurally and functionally different from the voltage-dependent K+ channels.
The family’s topology consists of two transmembrane domains that flank a single and highly conserved pore region with intracellular N- and C-termini. As is the case for the voltage-dependent K+ channels the functional unit for the Kir channels is composed of four subunits that can assembly as either homo or heterotetramers.
Kir channels are characterized by a K+ efflux that is limited by depolarizing membrane potentials thus making them essential for controlling resting membrane potential and K+ homeostasis.3
As its original name indicates (ROMK1 stands for Renal Outer Medullary K+ channel) Kir1.1 is strongly expressed in the kidney in the apical membrane of several kidney segments such as the thick ascending loop of Henle (TAL) and the cortical collecting duct (CCD). In addition, the channel is also expressed in the brain mainly in the cortex and hippocampus.3
Kir1.1 plays a key role in K+ recycling in the loop of Henle. Indeed, loss of function mutations in the Kir1.1 gene cause Bartter’s syndrome type II, a recessive autosomal disease characterized by the impairment of K+ efflux and the subsequent inability of the NKCC2 transporter to continue NaCl uptake. This leads to a high salt concentration in the urine that induces osmotic diuresis and low plasma volume.2
Pharmacologically, the Kir1.1 channel can be inhibited by several general K+ channel blockers such as Tertiapin (#STT-250), however the scorpion toxin Lq2 (#RTL-550) specifically and potently inhibits Kir1.1 channels.4
