Cloning, localization, and functional expression of a human brain inward rectifier potassium channel (hIRK1)

We have cloned a novel human brain inward rectifier K+ channel (hIRK1), which shares approximately 60% amino acid identity with another human inward rectifier (hIRK2) but 98% identity with the mouse IRK1. The hIRK1 mRNA is expressed in several human tissues: skeletal muscle > placenta > heart > brain > lung > kidney. In human brain, the hIRK1 mRNA is uniformly distributed (except for a higher level in the corpus callosum, which contains white matter and glial cells), whereas the hIRK2 mRNA is expressed in major regions of the basal ganglia and limbic system. Xenopus oocytes injected with hIRK1 cRNA expressed an inwardly rectifying K+ current that was blocked by extracellular Ba2+. The hIRK1 channel carried a significant outward current when membrane potential was more positive than the K+ equilibrium potential (EK) and therefore had an "N-shape" current-voltage relation, resembling that of the native cardiac IRK channel. The resting membrane potential was near EK in oocytes expressing hIRK1, but was approximately -40 mV in H2O-injected or non-injected oocytes. The ability of hIRK1 to set the resting membrane potential depended on the outward current. Single-channel conductance of hIRK1 was 32 pS measured with 150 mM KCl in the patch pipette, significantly higher than 23 pS measured for mouse IRK1 and approximately 10 pS for hIRK2.