scholarly journals Recruitment of Gβγ controls the basal activity of G‐protein coupled inwardly rectifying potassium (GIRK) channels: crucial role of distal C terminus of GIRK1

2014 ◽  
Vol 592 (24) ◽  
pp. 5373-5390 ◽  
Author(s):  
Uri Kahanovitch ◽  
Vladimir Tsemakhovich ◽  
Shai Berlin ◽  
Moran Rubinstein ◽  
Boaz Styr ◽  
...  
Keyword(s):  
G Protein ◽  
Crucial Role ◽  
Girk Channels ◽  
Basal Activity ◽  
C Terminus ◽  
Inwardly Rectifying ◽  
G Protein Coupled

scholarly journals Crucial Role of Neuron-enriched Endosomal Protein of 21 kDa in Sorting between Degradation and Recycling of Internalized G-protein-coupled Receptors

2004 ◽  
Vol 279 (34) ◽  
pp. 35687-35691 ◽  
Author(s):  
Colin Debaigt ◽  
Harald Hirling ◽  
Pascal Steiner ◽  
Jean-Pierre Vincent ◽  
Jean Mazella
Keyword(s):  
G Protein ◽  
Crucial Role ◽  
G Protein Coupled Receptors ◽  
G Protein Coupled

Neuroprotective action of daidzein: a crucial role of G-protein coupled receptor 30

2012 ◽  
Vol 64 (2) ◽  
pp. 465-466
Author(s):  
Kajta Małgorzata ◽  
Rzemieniec Joanna ◽  
Litwa Ewa ◽  
Lasoń Władysław
Keyword(s):  
G Protein ◽  
Crucial Role ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled ◽  
Neuroprotective Action

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

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.

Differential Effects of General Anesthetics on G Protein–coupled Inwardly Rectifying and Other Potassium Channels

2001 ◽  
Vol 95 (1) ◽  
pp. 144-153 ◽  
Author(s):  
Tomohiro Yamakura ◽  
Joanne M. Lewohl ◽  
R. Adron Harris
Keyword(s):  
Nitrous Oxide ◽  
Potassium Channels ◽  
G Protein ◽  
Volatile Anesthetics ◽  
General Anesthetics ◽  
Girk Channels ◽  
Intravenous Anesthetics ◽  
Amino Acid Mutations ◽  
Inwardly Rectifying ◽  
G Protein Coupled

Background General anesthetics differentially affect various families of potassium channels, and some potassium channels are suggested to be potential targets for anesthetics and alcohols. Methods The voltage-gated (ERG1, ELK1, and KCNQ2/3) and inwardly rectifying (GIRK1/2, GIRK1/4, GIRK2, IRK1, and ROMK1) potassium channels were expressed in Xenopus oocytes. Effects of volatile agents [halothane, isoflurane, enflurane, F3 (1-chloro-1,2,2-trifluorocyclobutane), and the structurally related nonimmobilizer F6 (1,2-dichlorohexafluorocyclobutane)], as well as intravenous (pentobarbital, propofol, etomidate, alphaxalone, ketamine), and gaseous (nitrous oxide) anesthetics and alcohols (ethanol and hexanol) on channel function were studied using a two-electrode voltage clamp. Results ERG1, ELK1, and KCNQ2/3 channels were either inhibited slightly or unaffected by concentrations corresponding to twice the minimum alveolar concentrations or twice the anesthetic EC50 of volatile and intravenous anesthetics and alcohols. In contrast, G protein-coupled inwardly rectifying potassium (GIRK) channels were inhibited by volatile anesthetics but not by intravenous anesthetics. The neuronal-type GIRK1/2 channels were inhibited by 2 minimum alveolar concentrations of halothane or F3 by 45 and 81%, respectively, whereas the cardiac-type GIRK1/4 channels were inhibited only by F3. Conversely, IRK1 and ROMK1 channels were completely resistant to all anesthetics tested. Current responses of GIRK2 channels activated by mu-opioid receptors were also inhibited by halothane. Nitrous oxide (approximately 0.6 atmosphere) slightly but selectively potentiated GIRK channels. Results of chimeric and multiple amino acid mutations suggest that the region containing the transmembrane domains, but not the pore-forming domain, may be involved in determining differences in anesthetic sensitivity between GIRK and IRK channels. Conclusions G protein-coupled inwardly rectifying potassium channels, especially those composed of GIRK2 subunits, were inhibited by clinical concentrations of volatile anesthetics. This action may be related to some side effects of these agents.

Sign Inversion in Photopharmacology: Incorporation of Cyclic Azobenzenes in Photoswitchable Potassium Channel Blockers and Openers

2019 ◽  
Author(s):  
Julie Trads ◽  
Katharina Hüll ◽  
Bryan Matsuura ◽  
Laura Laprell ◽  
Timm Fehrentz ◽  
...  
Keyword(s):  
G Protein ◽  
Biologically Active ◽  
Channel Blockers ◽  
Biological Applications ◽  
Girk Channels ◽  
Voltage Gated ◽  
Sign Inversion ◽  
Potassium Channel Blockers ◽  
Inwardly Rectifying ◽  
G Protein Coupled

Photopharmacology relies on ligands that change their pharmacodynamics upon photoisomerization. Many of these ligands are azobenzenes that are thermodynamically more stable in their elongated <i>trans</i>configuration, which predominates in the dark. Often, they are biologically active in this form and lose activity upon irradiation and photoisomerization to their <i>cis</i>-isomer. Recently, cyclic azobenzenes, so-called diazocines, have emerged. They are thermodynamically more stable in their bent <i>cis</i>­‑form than in their elongated <i>trans</i>-form. Incorporation of these switches into a variety of photopharmaceuticals could convert dark-active ligands into dark-inactive ligands, which is preferred in most biological applications. This “pharmacological sign-inversion” is demonstrated for a photochromic blocker of voltage-gated potassium channels, termed <b>CAL</b>, and a photochromic opener of G-protein-coupled inwardly rectifying potassium (GIRK) channels, termed <b>CLOGO</b>.<br>

Role of G protein–gated inwardly rectifying potassium channels in P2Y12 receptor–mediated platelet functional responses

Blood ◽  
2004 ◽  
Vol 104 (5) ◽  
pp. 1335-1343 ◽  
Author(s):  
Haripriya Shankar ◽  
Swaminathan Murugappan ◽  
Soochong Kim ◽  
Jianguo Jin ◽  
Zhongren Ding ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
G Protein ◽  
Shape Change ◽  
Human Platelets ◽  
P2y12 Receptor ◽  
Functional Responses ◽  
Girk Channels ◽  
Girk Channel ◽  
Inwardly Rectifying

Abstract The role of the Gi-coupled platelet P2Y12 receptor in platelet function has been well established. However, the functional effector or effectors contributing directly to αIIbβ3 activation in human platelets has not been delineated. As the P2Y12 receptor has been shown to activate G protein–gated, inwardly rectifying potassium (GIRK) channels, we investigated whether GIRK channels mediate any of the functional responses of the platelet P2Y12 receptor. Western blot analysis revealed that platelets express GIRK1, GIRK2, and GIRK4. In aspirin-treated and washed human platelets, 2 structurally distinct GIRK inhibitors, SCH23390 (R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride) and U50488H (trans-(±)-3,4-dichloro-N-methyl-N-[2-(pyrrolidinyl)cyclohexyl] benzeneacetamide methanesulfonate), inhibited adenosine diphosphate (ADP)–, 2-methylthioADP (2-MeSADP)–, U46619-, and low-dose thrombin–mediated platelet aggregation. However, the GIRK channel inhibitors did not affect platelet aggregation induced by high concentrations of thrombin, AYPGKF, or convulxin. Furthermore, the GIRK channel inhibitors reversed SFLLRN-induced platelet aggregation, inhibited the P2Y12-mediated potentiation of dense granule secretion and Akt phosphorylation, and did not affect the agonist-induced Gq-mediated platelet shape change and intracellular calcium mobilization. Unlike AR-C 69931MX, a P2Y12 receptor–selective antagonist, the GIRK channel blockers did not affect the ADP-induced adenlylyl cyclase inhibition, indicating that they do not directly antagonize the P2Y12 receptor. We conclude that GIRK channels are important functional effectors of the P2Y12 receptor in human platelets.

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