A structural determinant of differential sensitivity of cloned inward rectifier K+ channels to intracellular spermine.
Large subtype-specific differences in the sensitivity of cloned inward-rectifier K+ channels of the IRK1, BIR10 and ROMK1 subtype to being blocked by intracellular spermine (SPM) are described. It is shown, by site-directed mutagenesis, that the four orders of magnitude larger SPM sensitivity of BIR10 channels compared to ROMK1 channels may be explained by a difference in a single amino acid in the putative transmembrane segment TMII. This residue, a negatively charged glutamate in BIR10, is homologous to the residue in IRK1 and ROMK1 which has previously been shown to change gating properties and Mg2+ sensitivity. Differential block by physiological SPM concentrations is suggested as a major functional difference between subtypes of inward-rectifier K+ channels.
Fakler
B
B
Department of Sensory Biophysics, ENT-Hospital of the University of Tübingen, Germany.
Brändle
U
U
Bond
C
C
Glowatzki
E
E
König
C
C
Adelman
J P
JP
Zenner
H P
HP
Ruppersberg
J P
JP
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D008274:Magnesium / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D016297:Mutagenesis, Site-Directed; D009865:Oocytes / Q000502:physiology; D015221:Potassium Channels / Q000096:biosynthesis / Q000187:drug effects / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism; D013096:Spermine / Q000494:pharmacology* / Q000502:physiology; D013329:Structure-Activity Relationship; D014981:Xenopus; D000098854:Kcnj10 Channel
C510692:Kcnj1 protein, rat; D000098854:Kcnj10 Channel; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011994:Recombinant Proteins; D013096:Spermine; D008274:Magnesium