Approximately half of the NH2 terminus of inward rectifier (Kir) channels can be deleted without significant change in channel function, but activity is lost when more than ∼30 conserved residues before the first membrane spanning domain (M1) are removed. Systematic replacement of the positive charges in the NH2 terminus of Kir6.2 with alanine reveals several residues that affect channel function when neutralized. Certain mutations (R4A, R5A, R16A, R27A, R39A, K47A, R50A, R54A, K67A) change open probability, whereas an overlapping set of mutants (R16A, R27A, K39A, K47A, R50A, R54A, K67A) change ATP sensitivity. Further analysis of the latter set differentiates mutations that alter ATP sensitivity as a consequence of altered open state stability (R16A, K39A, K67A) from those that may affect ATP binding directly (K47A, R50A, R54A). The data help to define the structural determinants of Kir channel function, and suggest possible structural motifs within the NH2 terminus, as well as the relationship of the NH2 terminus with the extended cytoplasmic COOH terminus of the channel.

Original languageEnglish
Pages (from-to)437-446
Number of pages10
JournalJournal of General Physiology
Issue number3
StatePublished - Sep 2002


  • ATP
  • K
  • K current
  • Kir6.2
  • PIP


Dive into the research topics of 'The role of NH2-terminal positive charges in the activity of inward rectifier KATP channels'. Together they form a unique fingerprint.

Cite this