Two aspects of the inward rectification mechanism. Effects of cytoplasmic blockers and extracellular K+ on the inward rectifier K+ channel.
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 Ko+, the hypothesis that Ko+ 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 Ko+, is reviewed.
Kubo
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Y
Department of Neurophysiology, Tokyo Metropolitan Institute for Neuroscience, Japan.
D000818:Animals; D003593:Cytoplasm / Q000187:drug effects; D005110:Extracellular Space / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D015640:Ion Channel Gating / Q000502:physiology*; D008274:Magnesium / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009865:Oocytes; D018408:Patch-Clamp Techniques; D011073:Polyamines / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D014981:Xenopus
D011073:Polyamines; D015221:Potassium Channels; D008274:Magnesium