Abstract
Kir3 (or GIRK) channels have been known for nearly three decades to be activated by direct interactions with the βγ subunits of heterotrimeric G (Gαβγ) proteins in a membrane-delimited manner. Gα also interacts with GIRK channels and since PTX-sensitive Gα subunits show higher affinity of interaction they confer signaling specificity to G Protein- Coupled Receptors (GPCRs) that normally couple to these G protein subunits. In heterologous systems, overexpression of non PTX-sensitive Gα subunits scavenges the available Gβγ and biases GIRK activation through GPCRs that couple to these Gα subunits. Moreover, all Kir channels rely on their direct interactions with the phospholipid PIP2 to maintain their activity. Thus, signals that activate phospholipase C (e.g. through Gq signaling) to hydrolyze PIP2 result in inhibition of Kir channel activity. In this review, we illustrate with experiments performed in Xenopus oocytes that Kir channels can be used efficiently as reporters of GPCR function through Gi, Gs or Gq signaling. The membrane-delimited nature of this expression system makes it highly efficient for constructing dose-response curves yielding highly reproducible apparent affinities of different ligands for each GPCR tested.
Keywords: GPCR, GIRK, G protein, PIP2, TEVC, Xenopus oocytes.
Current Pharmaceutical Biotechnology
Title:G Protein-Coupled Receptor Signaling to Kir Channels in Xenopus Oocytes
Volume: 15 Issue: 10
Author(s): Candice Hatcher-Solis, Miguel Fribourg, Katerina Spyridaki, Jason Younkin, Amr Ellaithy, Guoqing Xiang, George Liapakis, Javier Gonzalez-Maeso, Hailin Zhang, Meng Cui and Diomedes E. Logothetis
Affiliation:
Keywords: GPCR, GIRK, G protein, PIP2, TEVC, Xenopus oocytes.
Abstract: Kir3 (or GIRK) channels have been known for nearly three decades to be activated by direct interactions with the βγ subunits of heterotrimeric G (Gαβγ) proteins in a membrane-delimited manner. Gα also interacts with GIRK channels and since PTX-sensitive Gα subunits show higher affinity of interaction they confer signaling specificity to G Protein- Coupled Receptors (GPCRs) that normally couple to these G protein subunits. In heterologous systems, overexpression of non PTX-sensitive Gα subunits scavenges the available Gβγ and biases GIRK activation through GPCRs that couple to these Gα subunits. Moreover, all Kir channels rely on their direct interactions with the phospholipid PIP2 to maintain their activity. Thus, signals that activate phospholipase C (e.g. through Gq signaling) to hydrolyze PIP2 result in inhibition of Kir channel activity. In this review, we illustrate with experiments performed in Xenopus oocytes that Kir channels can be used efficiently as reporters of GPCR function through Gi, Gs or Gq signaling. The membrane-delimited nature of this expression system makes it highly efficient for constructing dose-response curves yielding highly reproducible apparent affinities of different ligands for each GPCR tested.
Export Options
About this article
Cite this article as:
Hatcher-Solis Candice, Fribourg Miguel, Spyridaki Katerina, Younkin Jason, Ellaithy Amr, Xiang Guoqing, Liapakis George, Gonzalez-Maeso Javier, Zhang Hailin, Cui Meng and Logothetis E. Diomedes, G Protein-Coupled Receptor Signaling to Kir Channels in Xenopus Oocytes, Current Pharmaceutical Biotechnology 2014; 15 (10) . https://dx.doi.org/10.2174/1389201015666141031111916
DOI https://dx.doi.org/10.2174/1389201015666141031111916 |
Print ISSN 1389-2010 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4316 |
Call for Papers in Thematic Issues
Artificial Intelligence in Bioinformatics
Bioinformatics is an interdisciplinary field that analyzes and explores biological data. This field combines biology and information system. Artificial Intelligence (AI) has attracted great attention as it tries to replicate human intelligence. It has become common technology for analyzing and solving complex data and problems and encompasses sub-fields of machine ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Arterial Stiffness: A Novel Cardiovascular Risk Factor in Kidney Disease Patients
Current Vascular Pharmacology Cardiovascular Control After Spinal Cord Injury
Current Vascular Pharmacology The Role of Parthenolide in Intracellular Signalling Processes: Review of Current Knowledge
Current Signal Transduction Therapy Xanthine Oxidase Inhibitor Febuxostat as a Novel Agent Postulated to Act Against Vascular Inflammation
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Identification and Treatment of Patients with Homozygous Familial Hypercholesterolaemia: Information and Recommendations from a Middle East Advisory Panel
Current Vascular Pharmacology Management of Incidental Findings in the Era of Next-generation Sequencing
Current Genomics <i>Achillea millefolium</i> E.Mey: Phytochemistry and Pharmacological Profile
Current Traditional Medicine Cardiac Amyloidosis Responding to Bortezomib: Case Report and Review of Literature
Current Cardiology Reviews Cholesterol Lowering Therapy: Treat to Target or Reduce the Global Risk? The Unresolved Problem of Residual Risk
Current Pharmaceutical Design Analytical Procedures for Secondary Metabolites Determination: Recent Trends and Future Perspectives
Letters in Drug Design & Discovery Recent Advances in the Development of Small-molecule CCR5 Inhibitors for HIV
Mini-Reviews in Medicinal Chemistry Interception of Cocaine by Enzyme or Antibody Delivered with Viral Gene Transfer: A Novel Strategy for Preventing Relapse in Recovering Drug Users
CNS & Neurological Disorders - Drug Targets New Antibiotics for Severe ICU-Aquired Bacterial Infections
Infectious Disorders - Drug Targets Clinical Applications of Transcranial Doppler Sonography
Reviews on Recent Clinical Trials The Effects of Newer Beta-Adrenoceptor Antagonists on Vascular Function in Cardiovascular Disease
Current Vascular Pharmacology Experience with Androgen Deprivation Therapy for Prostate Cancer in Japan and Future Perspectives
Current Cancer Drug Targets Arterial Stiffness and Cardiovascular Drugs
Current Pharmaceutical Design Synthesis and Bioactivity of (R)-Ricinoleic Acid Derivatives: A Review
Current Medicinal Chemistry Long Term Ketamine and Ketamine Plus Alcohol Toxicity - What can we Learn from Animal Models?
Mini-Reviews in Medicinal Chemistry Evidence-Based Pharmacological Treatment of Substance Use Disorders and Pathological Gambling
Current Drug Abuse Reviews