Abstract
Important roles for connexins have emerged from studies linking connexin mutations to human disease. Use of connexins tagged with GFP have provided a clearer picture of the mechanisms that govern connexin channel function and it is now evident that functional forms of connexin channel include cell-cell channels and unapposed hemichannels. Clustering appears to be a requirement for opening of cell-cell channels and suggests that dynamic changes occur in plaques (clusters) as they form and grow that are critical for channel function. In particular, recruitment or generation of ‘silent’ channels has gained support as a mechanism by which coupling can be dynamically regulated within formed plaques. Two distinct voltage sensitive gating mechanisms appear to be built -into each hemichannel, one putatively located at the cytoplasmic entrance and the other at the extracellular end, each differing in sensitivity, kinetics and degree of channel/hemichannel closure. The extracellular gate may also be that whic h opens unapposed hemichannels in the plasma membrane and be the final target of many known chemical agents that act as uncouplers of cell-cell communication. An understanding of the structural requirements for regulation via gating and clustering represents an important preclinical step in the design of therapeutic agents to treat disorders arising from connexin channel and hemichannel dysfunction.
Current Drug Targets
Title: Connexin-GFPs Shed Light on Regulation of Cell-Cell Communication by Gap Junctions
Volume: 3 Issue: 6
Author(s): Vytas K. Verselis and Feliksas F. Bukauskas
Affiliation:
Abstract: Important roles for connexins have emerged from studies linking connexin mutations to human disease. Use of connexins tagged with GFP have provided a clearer picture of the mechanisms that govern connexin channel function and it is now evident that functional forms of connexin channel include cell-cell channels and unapposed hemichannels. Clustering appears to be a requirement for opening of cell-cell channels and suggests that dynamic changes occur in plaques (clusters) as they form and grow that are critical for channel function. In particular, recruitment or generation of ‘silent’ channels has gained support as a mechanism by which coupling can be dynamically regulated within formed plaques. Two distinct voltage sensitive gating mechanisms appear to be built -into each hemichannel, one putatively located at the cytoplasmic entrance and the other at the extracellular end, each differing in sensitivity, kinetics and degree of channel/hemichannel closure. The extracellular gate may also be that whic h opens unapposed hemichannels in the plasma membrane and be the final target of many known chemical agents that act as uncouplers of cell-cell communication. An understanding of the structural requirements for regulation via gating and clustering represents an important preclinical step in the design of therapeutic agents to treat disorders arising from connexin channel and hemichannel dysfunction.
Export Options
About this article
Cite this article as:
Vytas K. Verselis and Feliksas F. Bukauskas , Connexin-GFPs Shed Light on Regulation of Cell-Cell Communication by Gap Junctions, Current Drug Targets 2002; 3 (6) . https://dx.doi.org/10.2174/1389450023347272
DOI https://dx.doi.org/10.2174/1389450023347272 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
Call for Papers in Thematic Issues
New drug therapy for eye diseases
Eyesight is one of the most critical senses, accounting for over 80% of our perceptions. Our quality of life might be significantly affected by eye disease, including glaucoma, diabetic retinopathy, dry eye, etc. Although the development of microinvasive ocular surgery reduces surgical complications and improves overall outcomes, medication therapy is ...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
-
Circulating Endothelial Progenitor Cells as Biomarkers for Prediction of Cardiovascular Outcomes
Current Medicinal Chemistry Intra-Renal Hemodynamic Changes After Habitual Physical Activity in Patients with Chronic Kidney Disease
Current Pharmaceutical Design Clinical and Pre-clinical Applications of the Transcendental Meditation Program® in the Prevention and Treatment of Essential Hypertension and Cardiovascular Disease in Youth and Adults
Current Hypertension Reviews Novel Pharmacologic Approaches to the Management of Sepsis: Targeting the Host Inflammatory Response
Recent Patents on Inflammation & Allergy Drug Discovery Platelet-derived Growth Factor Receptor-beta is Differentially Regulated in Primary Mouse Pericytes and Brain Slices
Current Neurovascular Research Lipoprotein-Associated Phospholipase A2: How Effective as a Risk Marker of Cardiovascular Disease and as a Therapeutic Target?
Inflammation & Allergy - Drug Targets (Discontinued) Insulin-Like Growth Factor 1 Receptor Targeted Therapeutics: Novel Compounds and Novel Treatment Strategies for Cancer Medicine
Recent Patents on Anti-Cancer Drug Discovery The Effects of Olprinone, a Phosphodiesterase 3 Inhibitor, on Systemic and Cerebral Circulation
Current Vascular Pharmacology Bioactive Peptides - Are There More Antihypertensive Mechanisms Beyond ACE Inhibition?
Current Pharmaceutical Design Hypomagnesaemia/Hypokalemia Associated with the Use of Esomeprazole
Current Drug Safety Inhibition of the Calcineurin-NFAT Signalling Cascade in the Treatment of Heart Failure
Recent Patents on Cardiovascular Drug Discovery Pregabalin in Neuropathic Pain: Evidences and Possible Mechanisms
Current Neuropharmacology Novel Molecular Targets in the Treatment of Cardiac Hypertrophy
Recent Patents on Cardiovascular Drug Discovery Nanofibers Based Tissue Engineering and Drug Delivery Approaches for Myocardial Regeneration
Current Pharmaceutical Design Hepatic Injury to the Newborn Liver Due to Drugs
Current Pharmaceutical Design Development and Clinical use of Prasugrel and Ticagrelor
Current Pharmaceutical Design Therapeutic microRNA Delivery Strategies with Special Emphasis on Cancer Therapy and Tumorigenesis: Current Trends and Future Challenges
Current Drug Metabolism Allergic Asthma: A Summary from Genetic Basis, Mouse Studies, to Diagnosis and Treatment
Current Pharmaceutical Design Orai1 and Transient Receptor Potential Channels as Novel Molecular Targets to Impair Tumor Neovascularization in Renal Cell Carcinoma and other Malignancies
Anti-Cancer Agents in Medicinal Chemistry The Interactions of Anticancer Agents with Tea Catechins: Current Evidence from Preclinical Studies
Anti-Cancer Agents in Medicinal Chemistry