Abstract
ATP-sensitive K+ channels (KATP channels) regulate insulin secretion by coupling intracellular metabolic changes to excitability of the plasma membrane in pancreatic β-cells. The channels are closed when extracellular glucose levels are elevated due to enhanced feature. By contrast, cardiac-type KATP channels, which open in response to metabolic stress during cardiac ischemia, shorten action potential durations. This may contribute to the cardioprotection by decreasing Ca2+ influx through sarcolemma. By sensing intracellular ATP levels or ATP / ADP ratios, changes in activity of KATP channels convert metabolic information into membrane excitability. In addition to channel regulation by nucleotide concentrations, the channel activity is also dependent on the concentrations of membrane phospholipids, including phosphatidyl inositol-4,5-bisphosphate (PIP2). The levels of PIP2 in the membrane may determine the basal activity of the channels. This suggests that channel activity would be modulated by the pathway of receptor-coupled GTPbinding protein (G-protein) and phosphatidyl inositol phospholipase C (PI-PLC) stimulation, which brings about depletion of the membrane PIP2 pool. Thus, KATP channels not only provide interface of metabolic changes with electrical excitation, but also rapidly transmit extracellular signals through receptor-coupled Gprotein and PI-PLC pathway via PIP2 metabolism.
Keywords: atp-sensitive channel, insulin secretion, inwardly rectifying channel, pancreatic, phospholipid, sulfonylurea receptor
Current Medicinal Chemistry
Title: Receptor-Operated Regulation of ATP-Sensitive K+ Channels Via Membrane Phospholipid Metabolism
Volume: 10 Issue: 3
Author(s): M. Kakei
Affiliation:
Keywords: atp-sensitive channel, insulin secretion, inwardly rectifying channel, pancreatic, phospholipid, sulfonylurea receptor
Abstract: ATP-sensitive K+ channels (KATP channels) regulate insulin secretion by coupling intracellular metabolic changes to excitability of the plasma membrane in pancreatic β-cells. The channels are closed when extracellular glucose levels are elevated due to enhanced feature. By contrast, cardiac-type KATP channels, which open in response to metabolic stress during cardiac ischemia, shorten action potential durations. This may contribute to the cardioprotection by decreasing Ca2+ influx through sarcolemma. By sensing intracellular ATP levels or ATP / ADP ratios, changes in activity of KATP channels convert metabolic information into membrane excitability. In addition to channel regulation by nucleotide concentrations, the channel activity is also dependent on the concentrations of membrane phospholipids, including phosphatidyl inositol-4,5-bisphosphate (PIP2). The levels of PIP2 in the membrane may determine the basal activity of the channels. This suggests that channel activity would be modulated by the pathway of receptor-coupled GTPbinding protein (G-protein) and phosphatidyl inositol phospholipase C (PI-PLC) stimulation, which brings about depletion of the membrane PIP2 pool. Thus, KATP channels not only provide interface of metabolic changes with electrical excitation, but also rapidly transmit extracellular signals through receptor-coupled Gprotein and PI-PLC pathway via PIP2 metabolism.
Export Options
About this article
Cite this article as:
Kakei M., Receptor-Operated Regulation of ATP-Sensitive K+ Channels Via Membrane Phospholipid Metabolism, Current Medicinal Chemistry 2003; 10 (3) . https://dx.doi.org/10.2174/0929867033368475
DOI https://dx.doi.org/10.2174/0929867033368475 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...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
- Announcements
Related Articles
-
Nanoparticle Therapy for Allergic and Inflammatory Disease
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Assessment of Persistent, Bioaccumulative and Toxic Organic Environmental Pollutants in Liver and Adipose Tissue of Alzheimer’s Disease Patients and Age-matched Controls
Current Alzheimer Research A Comprehensive Review on Preclinical Diabetic Models
Current Diabetes Reviews Role of Endothelial Nitric Oxide in Cerebrovascular Regulation
Current Pharmaceutical Biotechnology The Akt/PKB Family of Protein Kinases: A Review of Small Molecule Inhibitors and Progress Towards Target Validation
Current Topics in Medicinal Chemistry Cannabis Abuse and Vulnerability to Psychosis: Targeting Preventive Services
Current Pharmaceutical Design Cholinesterase Biosensor Construction – A Review
Protein & Peptide Letters Actinomycetes as a Paramount Source of Biologically Important Enzyme Inhibitors – “A Boon to Mankind”
Current Bioactive Compounds Clinical Utility of Biomarkers in Premature Atherosclerosis
Current Medicinal Chemistry Quantitative Gait Disturbances in Older Adults with Cognitive Impairments
Current Pharmaceutical Design Gene Therapy of Cancer Based on Interleukin 12
Current Gene Therapy Arterial Accelerated Aging in Dialysis Patients: The Clinical Impact of Vascular Calcification
Current Vascular Pharmacology Endothelial (Dys)Function in Lone Atrial Fibrillation
Current Pharmaceutical Design Immune-non Immune Networks in Intestinal Inflammation
Current Drug Targets Biocompatible Delivery System for Metformin: Characterization, Radiolabeling and In Vitro Studies
Anti-Cancer Agents in Medicinal Chemistry Withdrawn: Effect of Fractions of Vernonia amygdalina on Some Biochemical Parameters in High Fat Diet-Induced Obese Rats
Endocrine, Metabolic & Immune Disorders - Drug Targets The Role of Antiplatelet Therapy in Primary Prevention. A Review
Current Pharmaceutical Design Coffee: A Dietary Intervention on Type 2 Diabetes?
Current Medicinal Chemistry Peptides for In Vivo Target-Specific Cancer Imaging
Mini-Reviews in Medicinal Chemistry Preeclampsia and the Future Development of Cardiovascular Disease: A Review
Current Women`s Health Reviews