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A C‐terminal peptide of the GIRK1 subunit directly blocks the G protein‐activated K + channel (GIRK) expressed in Xenopus oocytes
Author(s) -
Luchian Tudor,
Dascal Nathan,
Dessauer Carmen,
Platzer Dieter,
Davidson Norman,
Lester Henry A.,
Schreibmayer Wolfgang
Publication year - 1997
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.1997.013bc.x
Subject(s) - g protein coupled inwardly rectifying potassium channel , xenopus , g protein , peptide , protein subunit , potassium channel , inward rectifier potassium ion channel , chemistry , biophysics , microbiology and biotechnology , biology , ion channel , biochemistry , receptor , gene
1 In order to find out the functional roles of cytosolic regions of a G protein‐activated, inwardly rectifying potassium channel subunit we studied block of GIRK channels, expressed in Xenopus laevis oocytes, by synthetic peptides in isolated inside‐out membrane patches. 2 A peptide (DS6) derived from the very end of the C‐terminus of GIRK1 reversibly blocked GIRK activity with IC 50 values of 7.9 ± 2.0 or 3.5 ± 0.5 μg ml −1 (corresponding to 3.7 ± 0.9 or 1.7 ± 0.2 μmol l −1 ) for GIRK1/GIRK5 or GIRK1/GIRK4 channels, respectively. 3 Dose dependency studies of GIRK activation by purified βγ subunits of the G protein (G βγ ) showed that DS6 block of GIRK channels is not the result of competition of the peptide with functional GIRK channels for the available G βγ . 4 Burst duration of GIRK channels was reduced, whereas long closed times between bursts were markedly increased, accounting for the channel block observed. 5 Block by the DS6 peptide was slightly voltage dependent, being stronger at more negative potentials. 6 These data support the hypothesis that the distal part of the carboxy‐terminus of GIRK1 is a part of the intrinsic gate that keeps GIRK channels closed in the absence of G βγ .