MOLECULAR AND FUNCTIONAL-HETEROGENEITY OF INWARD RECTIFIER POTASSIUM CHANNELS IN BRAIN AND HEART

We have cloned three background inward rectifier potassium channels wi th two transmembrane regions from mouse brain cDNA library. We designa ted them mouse brain (MB) IRK1, IRK2, and IRK3, based on their amino a cid sequences and the electrophysiological properties of currents expr essed in Xenopus oocytes. Xenopus oocytes injected with cRNAs derived from these clones expressed K+ currents, which showed classical inward rectifier potassium channel characteristics at the whole cell current level and were blocked by Ba2+ and Cs+ in a concentration- and voltag e-dependent manner. The single-channel recordings revealed, however, t hat the unitary conductance of IRK1 was similar to 22pS; IRK2, similar to 34pS; and IRK3, similar to 12pS. By Northern blot analysis, IRK1 p redominantly was expressed in the forebrain rather than in the cerebel lum, and vice versa in the case of IRK2. IRK3 was expressed specifical ly in the forebrain. On the other hand, IRK1 and IRK2, but not IRK3, w ere expressed in the heart. These results indicate the heterogeneity o f the molecular structure and functional role of two transmembrane reg ion types of background inward rectifier potassium channels in the bra in and heart.