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 in wardly rectifying potassium channels (IRK1, GIRK1, and ROMK1, 60, 42, and 37%, respectively) and has a similar proposed topology of two memb rane spanning domains that correspond to the inner core structure of v oltage 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 picosie mens by both direct measurement and noise analysis, in 102 mM external [K+]. HRK1 currents were blocked by external Ba2+ and Cs+ (K(0) = 183 mu M, and K(-130) = 30 mu M, respectively), and internal tetraethylam monium ion (K(0) = 62 mu M), but were insensitive to external tetraeth ylammonium ion. The functional properties of HRK1 are very similar to those of glial cell inward rectifier K+ channels and HRK1 may represen t a glial cell inward rectifier.