Cloning and expression of a novel human brain inward rectifier potassium channel

A complementary DNA encoding an inward rectifier K⁺ channel (HRK1) was isolated from human hippocampus using a 392-base pair cDNA (HHCMD37) as a probe. HRK1 shows sequence similarity to three recently cloned inwardly rectifying potassium channels (IRK1, GIRK1, and ROMK1, 60, 42, and 37%, respectively) and has a similar proposed topology of two membrane spanning domains that correspond to the inner core structure of voltage gated K⁺ channels. When HRK1 was expressed in Xenopus oocytes, large inward K⁺ currents were observed below the K⁺ reversal potential but very little outward K⁺ current was observed. In on-cell membrane patches, single channel conductance (g) was estimated to be 10 picosiemens by both direct measurement and noise analysis, in 102 mM external [K⁺]. HRK1 currents were blocked by external Ba²⁺ and Cs⁺ (K(0) = 183 μM, and K(-130) = 30 μM, respectively), and internal tetraethylammonium ion (K(0) = 62 μM), but were insensitive to external tetraethylammonium ion. The functional properties of HRK1 are very similar to those of glial cell inward rectifier K⁺ channels and HRK1 may represent a glial cell inward rectifier.