Two Aspects of the Inward Rectification MechanismEffects of Cytoplasmic Blockers and Extracellular K+ on the Inward Rectifier K+ Channel

摘要

The inward rectification of the inward rectifier K+ channels has been reported to be caused by both the block of the outward current by cytoplasmic Mg2+ and by intrinsic channel gating. Recently it was uncovered that the apparent intrinsic gating is mostly due to a block by cytoplasmic polyamines which is actually extrinsic to the channel. Furthermore, negatively charged amino-acid residues in the center of the M2 region and in the C-terminal hydrophilic domain were identified to be involved in the binding of these blockers to the channels, The inward rectifier shows consistent inward rectification at various extracellular K+ concentrations ([K+]o). To explain the dependency of the channel activity on K+o, the hypothesis that K+o interacts with the inward rectifier K+ channel and thereby activates it (K+-activated K+ channel model) has been postulated. In this manuscript, the history and recent progresses of the study of the inward rectification mechanism, especially the effect of the cytoplasmic blockers and K+o, is reviewed.