XB-ART-15683
J Physiol
November 15, 1997;
505 ( Pt 1)
13-22.
A C-terminal peptide of the GIRK1 subunit directly blocks the G protein-activated K+ channel (GIRK) expressed in Xenopus oocytes.
Luchian T
,
Dascal N
,
Dessauer C
,
Platzer D
,
Davidson N
,
Lester HA
,
Schreibmayer W
.
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 IC50 values of 7.9 +/- 2.0 or 3.5 +/- 0.5 micrograms
ml-1 (corresponding to 3.7 +/- 0.9 or 1.7 +/- 0.2 mumol l-1) for
GIRK1/GIRK5 or
GIRK1/
GIRK4 channels, respectively. 3. Dose dependency studies of
GIRK activation by purified beta gamma subunits of the G protein (G beta gamma) showed that DS6 block of
GIRK channels is not the result of competition of the peptide with functional
GIRK channels for the available G beta gamma. 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 beta gamma.
PubMed ID:
9409468
PMC ID:
PMC1160090
Article link:
J Physiol
Species referenced:
Xenopus
Genes referenced:
il17f
kcnj3
kcnj5
References [+] :
Ashford,
Cloning and functional expression of a rat heart KATP channel.
1996,
Pubmed
Ashford,
Cloning and functional expression of a rat heart KATP channel.
1996,
Pubmed
Cohen,
Inhibition of an inward rectifier potassium channel (Kir2.3) by G-protein betagamma subunits.
1997,
Pubmed
,
Xenbase
Dascal,
Atrial G protein-activated K+ channel: expression cloning and molecular properties.
1993,
Pubmed
,
Xenbase
Dascal,
Inhibition of function in Xenopus oocytes of the inwardly rectifying G-protein-activated atrial K channel (GIRK1) by overexpression of a membrane-attached form of the C-terminal tail.
1995,
Pubmed
,
Xenbase
Doupnik,
The inward rectifier potassium channel family.
1995,
Pubmed
Ficker,
Spermine and spermidine as gating molecules for inward rectifier K+ channels.
1994,
Pubmed
,
Xenbase
Ho,
Cloning and expression of an inwardly rectifying ATP-regulated potassium channel.
1993,
Pubmed
,
Xenbase
Hoshi,
Biophysical and molecular mechanisms of Shaker potassium channel inactivation.
1990,
Pubmed
,
Xenbase
Huang,
Evidence that direct binding of G beta gamma to the GIRK1 G protein-gated inwardly rectifying K+ channel is important for channel activation.
1995,
Pubmed
,
Xenbase
Ivanova-Nikolova,
Effector contributions to G beta gamma-mediated signaling as revealed by muscarinic potassium channel gating.
1997,
Pubmed
Koch,
The binding site for the beta gamma subunits of heterotrimeric G proteins on the beta-adrenergic receptor kinase.
1993,
Pubmed
Kofuji,
Evidence that neuronal G-protein-gated inwardly rectifying K+ channels are activated by G beta gamma subunits and function as heteromultimers.
1995,
Pubmed
,
Xenbase
Kozasa,
Purification of recombinant G proteins from Sf9 cells by hexahistidine tagging of associated subunits. Characterization of alpha 12 and inhibition of adenylyl cyclase by alpha z.
1995,
Pubmed
Krapivinsky,
The G-protein-gated atrial K+ channel IKACh is a heteromultimer of two inwardly rectifying K(+)-channel proteins.
1995,
Pubmed
,
Xenbase
Krapivinsky,
G beta gamma binds directly to the G protein-gated K+ channel, IKACh.
1996,
Pubmed
Kubo,
Primary structure and functional expression of a mouse inward rectifier potassium channel.
1993,
Pubmed
,
Xenbase
Kunkel,
Identification of domains conferring G protein regulation on inward rectifier potassium channels.
1996,
Pubmed
,
Xenbase
Kurachi,
G protein regulation of cardiac muscarinic potassium channel.
1995,
Pubmed
Nair,
Cardiac muscarinic potassium channel activity is attenuated by inhibitors of G beta gamma.
1995,
Pubmed
North,
Twelfth Gaddum memorial lecture. Drug receptors and the inhibition of nerve cells.
1989,
Pubmed
Pessia,
Contributions of the C-terminal domain to gating properties of inward rectifier potassium channels.
1995,
Pubmed
Reuveny,
Activation of the cloned muscarinic potassium channel by G protein beta gamma subunits.
1994,
Pubmed
,
Xenbase
Reuveny,
Inactivation of a G protein-coupled inwardly rectifying K+ channel.
1998,
Pubmed
,
Xenbase
Sakmann,
Acetylcholine activation of single muscarinic K+ channels in isolated pacemaker cells of the mammalian heart.
1983,
Pubmed
Schreibmayer,
Voltage clamping of Xenopus laevis oocytes utilizing agarose-cushion electrodes.
1994,
Pubmed
,
Xenbase
Schreibmayer,
Inhibition of an inwardly rectifying K+ channel by G-protein alpha-subunits.
1996,
Pubmed
,
Xenbase
Slesinger,
Identification of structural elements involved in G protein gating of the GIRK1 potassium channel.
1995,
Pubmed
,
Xenbase
Wickman,
Recombinant G-protein beta gamma-subunits activate the muscarinic-gated atrial potassium channel.
1994,
Pubmed
Wickman,
Ion channel regulation by G proteins.
1995,
Pubmed
