scholarly journals Emerging roles for G protein-gated inwardly rectifying potassium (GIRK) channels in health and disease

2010 ◽  
Vol 11 (5) ◽  
pp. 301-315 ◽  
Author(s):  
Christian Lüscher ◽  
Paul A. Slesinger
Keyword(s):  
G Protein ◽  
Girk Channels ◽  
Health And Disease ◽  
Inwardly Rectifying

Involvement of G-protein-activated inwardly rectifying K+ (GIRK) channels in opioid-induced analgesia

2000 ◽  
Vol 38 (1) ◽  
pp. 113-116 ◽  
Author(s):  
Kazutaka Ikeda ◽  
Toru Kobayashi ◽  
Toshiro Kumanishi ◽  
Hiroaki Niki ◽  
Ryoji Yano
Keyword(s):  
G Protein ◽  
Girk Channels ◽  
Inwardly Rectifying

scholarly journals Activation of G-protein-gated inwardly rectifying potassium (Kir3/GirK) channels rescues hippocampal functions in a mouse model of early amyloid-β pathology

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Irene Sánchez-Rodríguez ◽  
Sara Temprano-Carazo ◽  
Alberto Nájera ◽  
Souhail Djebari ◽  
Javier Yajeya ◽  
...  
Keyword(s):  
Mouse Model ◽  
G Protein ◽  
Amyloid Β ◽  
Girk Channels ◽  
Inwardly Rectifying

scholarly journals Suprachiasmatic nucleus function and circadian entrainment are modulated by G protein‐coupled inwardly rectifying (GIRK) channels

2014 ◽  
Vol 592 (22) ◽  
pp. 5079-5092 ◽  
Author(s):  
L. M. Hablitz ◽  
H. E. Molzof ◽  
J. R. Paul ◽  
R. L. Johnson ◽  
K. L. Gamble
Keyword(s):  
G Protein ◽  
Suprachiasmatic Nucleus ◽  
Girk Channels ◽  
Inwardly Rectifying ◽  
G Protein Coupled

Rapid desensitization of G protein-gated inwardly rectifying K+ currents is determined by G protein cycle

2004 ◽  
Vol 287 (1) ◽  
pp. C182-C191 ◽  
Author(s):  
Joanne L. Leaney ◽  
Amy Benians ◽  
Sean Brown ◽  
Muriel Nobles ◽  
David Kelly ◽  
...  
Keyword(s):  
G Protein ◽  
Competitive Inhibition ◽  
Similar Degree ◽  
Channel Activation ◽  
Girk Channels ◽  
Membrane Hyperpolarization ◽  
Hek 293 ◽  
Fast Activation ◽  
Inwardly Rectifying ◽  
Stimulation Of

Activation of G protein-gated inwardly rectifying K+ (GIRK) channels, found in the brain, heart, and endocrine tissue, leads to membrane hyperpolarization that generates neuronal inhibitory postsynaptic potentials, slows the heart rate, and inhibits hormone release. During stimulation of Gi/o-coupled receptors and subsequent channel activation, it has been observed that the current desensitizes. In this study we examined mechanisms underlying fast desensitization of cloned heteromeric neuronal Kir3.1+3.2A and atrial Kir3.1+3.4 channels and also homomeric Kir3.0 currents in response to stimulation of several Gi/o G protein-coupled receptors (GPCRs) expressed in HEK-293 cells (adenosine A1, adrenergic α2A, dopamine D2S, M4 muscarinic, and GABAB1b/2 receptors). We found that all agonist-induced currents displayed a similar degree of desensitization except the adenosine A1 receptor, which exhibits an additional desensitizing component. Using the nonhydrolyzable GTP analog guanosine 5′- O-(3-thiotriphosphate) (GTPγS), we found that this is due to a receptor-dependent, G protein-independent process. Using Ca2+ imaging we showed that desensitization is unlikely to be accounted for solely by phospholipase C activation and phosphatidylinositol 4,5-bisphosphate (PIP2) hydrolysis. We examined the contribution of the G protein cycle and found the following. First, agonist concentration is strongly correlated with degree of desensitization. Second, competitive inhibition of GDP/GTP exchange by using nonhydrolyzable guanosine 5′- O-(2-thiodiphosphate) (GDPβS) has two effects, a slowing of channel activation and an attenuation of the fast desensitization phenomenon. Finally, using specific Gα subunits we showed that ternary complexes with fast activation rates display more prominent desensitization than those with slower activation kinetics. Together our data suggest that fast desensitization of GIRK currents is accounted for by the fundamental properties of the G protein cycle.

scholarly journals A novel ion conducting route besides the central pore in an inherited mutant of G-protein-gated inwardly rectifying K+ channel

2021 ◽  
Author(s):  
I-Shan Chen ◽  
Jodene Eldstrom ◽  
David Fedida ◽  
Yoshihiro Kubo
Keyword(s):  
G Protein ◽  
Structural Changes ◽  
Single Channel ◽  
Ion Selectivity ◽  
K Channel ◽  
Girk Channels ◽  
Electrode Voltage ◽  
Ion Conducting ◽  
Inwardly Rectifying ◽  
Better Than

G-protein-gated inwardly rectifying K+ (GIRK; Kir3.x) channels play important physiological roles in various organs. Some of the disease-associated mutations of GIRK channels are known to induce loss of K+ selectivity but their structural changes remain unclear. In this study, we investigated the mechanisms underlying the abnormal ion selectivity of inherited GIRK mutants. By the two-electrode voltage-clamp analysis of GIRK mutants heterologously expressed in Xenopus oocytes, we observed that Kir3.2 G156S permeates Li+ better than Rb+, while T154del or L173R of Kir3.2 and T158A of Kir3.4 permeate Rb+ better than Li+, suggesting a unique conformational change in the G156S mutant. Applications of blockers of the selectivity filter (SF) pathway, Ba2+ or Tertiapin-Q (TPN-Q), remarkably increased the Li+-selectivity of Kir3.2 G156S but did not alter those of the other mutants. In single-channel recordings of Kir3.2 G156S expressed in mouse fibroblasts, two types of events were observed, one attributable to a TPN-Q sensitive K+ current and the second a TPN-Q resistant Li+ current. The results show that a novel Li+ permeable and blocker-resistant pathway exists in G156S in addition to the SF pathway. Mutations in the pore helix (PH), S148F and T151A, also induced high Li+ permeation. Our results demonstrate that the mechanism underlying the loss of K+ selectivity of Kir3.2 G156S involves formation of a novel ion permeation pathway besides the SF pathway, which allows permeation of various species of cations.

scholarly journals The Expression and Localisation of G-Protein-Coupled Inwardly Rectifying Potassium (GIRK) Channels Is Differentially Altered in the Hippocampus of Two Mouse Models of Alzheimer’s Disease

2021 ◽  
Vol 22 (20) ◽  
pp. 11106
Author(s):  
Rocío Alfaro-Ruiz ◽  
Alejandro Martín-Belmonte ◽  
Carolina Aguado ◽  
Félix Hernández ◽  
Ana Esther Moreno-Martínez ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Transgenic Mice ◽  
G Protein ◽  
Hippocampal Neurons ◽  
Quantitative Description ◽  
Pyramidal Cells ◽  
Subcellular Localisation ◽  
Girk Channels ◽  
Ca1 Pyramidal Cells ◽  
Inwardly Rectifying

G protein-gated inwardly rectifying K+ (GIRK) channels are the main targets controlling excitability and synaptic plasticity on hippocampal neurons. Consequently, dysfunction of GIRK-mediated signalling has been implicated in the pathophysiology of Alzheimer´s disease (AD). Here, we provide a quantitative description on the expression and localisation patterns of GIRK2 in two transgenic mice models of AD (P301S and APP/PS1 mice), combining histoblots and immunoelectron microscopic approaches. The histoblot technique revealed differences in the expression of GIRK2 in the two transgenic mice models. The expression of GIRK2 was significantly reduced in the hippocampus of P301S mice in a laminar-specific manner at 10 months of age but was unaltered in APP/PS1 mice at 12 months compared to age-matched wild type mice. Ultrastructural approaches using the pre-embedding immunogold technique, demonstrated that the subcellular localisation of GIRK2 was significantly reduced along the neuronal surface of CA1 pyramidal cells, but increased in its frequency at cytoplasmic sites, in both P301S and APP/PS1 mice. We also found a decrease in plasma membrane GIRK2 channels in axon terminals contacting dendritic spines of CA1 pyramidal cells in P301S and APP/PS1 mice. These data demonstrate for the first time a redistribution of GIRK channels from the plasma membrane to intracellular sites in different compartments of CA1 pyramidal cells. Altogether, the pre- and post-synaptic reduction of GIRK2 channels suggest that GIRK-mediated alteration of the excitability in pyramidal cells could contribute to the cognitive dysfunctions as described in the two AD animal models.

Human Adrenal Glomerulosa Cells Express K2P and GIRK Potassium Channels that are inhibited by AngII and ACTH

2021 ◽  
Author(s):  
John J. Enyeart ◽  
Judith A. Enyeart
Keyword(s):  
G Protein ◽  
Zona Glomerulosa ◽  
Time Dependent ◽  
Aldosterone Secretion ◽  
Girk Channels ◽  
Whole Cell ◽  
Whole Cell Patch Clamp ◽  
Girk Channel ◽  
Inwardly Rectifying ◽  
G Protein Coupled

In whole-cell patch clamp recordings, it was discovered that normal human adrenal zona glomerulosa (AZG) cells express members of the three major families of K+ channels. Among these are a two pore (K2P) leak-type and a G-protein-coupled, inwardly-rectifying (GIRK) channel, both inhibited by peptide hormones that stimulate aldosterone secretion. The K2P current displayed properties identifying it as TREK-1 (KCNK2). This outwardly-rectifying current was activated by arachidonic acid and inhibited by angiotensin II (AngII), adrenocorticotrophic hormone (ACTH), and forskolin. The activation and inhibition of TREK-1 was coupled to AZG cell hyperpolarization and depolarization, respectively. A second K2P channel, TASK-1 (KCNK3), was expressed at a lower density in AZG cells. Human AZG cells also express inwardly rectifying K+ current(s) (KIR) that include quasi-instantaneous and time-dependent components. This is the first report demonstrating the presence of KIR in whole cell recordings from AZG cells of any species. The time-dependent current was selectively inhibited by AngII, and ACTH, identifying it as a G protein-coupled (GIRK) channel, most likely KIR3.4 (KCNJ5). The quasi-instantaneous KIR current was not inhibited by AngII or ACTH, and may be a separate non-GIRK current. Finally, AZG cells express a voltage-gated, rapidly inactivating K+ current whose properties identified as KV1.4 (KCNA4), a conclusion confirmed by Northern blot. These findings demonstrate that human AZG cells express K2P and GIRK channels whose inhibition by AngII and ACTH are likely coupled to depolarization-dependent secretion. They further demonstrate that human AZG K+ channels differ fundamentally from the widely adopted rodent models for human aldosterone secretion.

scholarly journals A G-protein-activated inwardly rectifying K+ channel (GIRK4) from human hippocampus associates with other GIRK channels

1996 ◽  
Vol 16 (3) ◽  
pp. 930-938 ◽  
Author(s):  
A Spauschus ◽  
KU Lentes ◽  
E Wischmeyer ◽  
E Dissmann ◽  
C Karschin ◽  
...  
Keyword(s):  
G Protein ◽  
K Channel ◽  
Girk Channels ◽  
Human Hippocampus ◽  
Inwardly Rectifying
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