Molecular and functional heterogeneity of inward rectifier potassium channels in brain and heart.

We have cloned cDNAs encoding three background inward rectifier potassium channels from a mouse brain cDNA library. We designated them mouse brain (MB)- IRK1, MB-IRK2, and MB-IRK3, based on their amino acid sequences and the electrophysiological properties of currents expressed in Xenopus oocytes. Xenopus oocytes injected with cRNAs derived from these clones expressed K+ currents that showed classical inward rectifier potassium channel characteristics at whole cell current level and that were blocked by Ba2+ and Ca+ in a concentration- and voltage- dependent manner. The single channel recordings revealed, however, that the unitary conductance of MB-IRKI was approximately 22pS; MB-IRK2, approximately 34pS; and MB-IRK3, approximately 12pS. By Northern blot analysis, MB-IRKI was more predominantly expressed in forebrain than in cerebellum, and vice versa in the case MB-IRK2. MB-IRK3 was expressed specifically in forebrain. On the other hand, MB-IRK1 and MB-IRK2, but not MB-IRK3, were expressed in heart. These results indicate the heterogeneity of the molecular structure and functional role of the two transmembrane region type of background inward rectifier potassium channels in brain and heart.