抄録
Homomeric and heteromeric isoforms of the human inward-rectifier K+ channels Kir4.1 and Kir5.1 are essential to K+ regulation in the kidney and the brain. This study establishes the current-voltage relationship, inward rectification, sensitivity to pH and known Kir channel blockers, K+ selectivity, and several single-channel properties of these channels using the patch-clamp technique. Identical experiments were conducted with cells expressing either Kir4.1 alone or co-expressing Kir4.1 and Kir5.1 (mass ration 1:5), as homomeric Kir5.1 is non-functional. Our data present Kir4.1 and Kir4.1/5.1 channels as functionally distinct proteins, consistent with previous work on orthologous channels. In contrast to strongly-rectifying Kir4.1/5.1 heteromers, homomeric Kir4.1 channels rectify only moderately, have a higher open probability, lower (non-burst) single-channel conductance, and are less susceptible to rundown. Sensitivity to Kir channels blockers (BaCl2 >> CsCl) and extracellular pH was comparable. Based on this functional separation and recent reports of distinct distribution and expression onset in the brain, we propose that Kir4.1 and Kir4.1/5.1 channels engage in distinct physiological functions that make them likely candidates for excitability disorders in humans. Supported by The Kanehara Foundation (CL), the Japanese Ministry of Education, Science, Sports, and Culture: Grant-in-aid for specific research in a priority area (HH, YK). [Jpn J Physiol 55 Suppl:S139 (2005)]
