Please wait, while we are loading the content...
Please wait, while we are loading the content...
| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Cooper, Michelle A. Deeb, Tarek Z. Lambert, Jeremy J. Livesey, Matthew R. Kozuska, Janna Hales, Tim G. Carland, Jane E. Peters, John A. |
| Description | Author Affiliation: Livesey MR ( Neurosciences Institute, Division of Pathology and Neuroscience, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland, United Kingdom.) |
| Abstract | Cation-selective cysteine (Cys)-loop transmitter-gated ion channels provide an important pathway for $Ca^{2+}$ entry into neurones. We examined the influence on $Ca^{2+}$ permeation of amino acids located at intra- and extracellular ends of the conduction pathway of the human 5-hydroxytryptamine type 3A $(5-HT_{3A})$ receptor. Mutation of cytoplasmic arginine residues 432, 436, and 440 to glutamine, aspartate, and alanine (the aligned residues of the human $5-HT_{3B}$ subunit (yielding $5-HT_{3A}(QDA))$ increased $P_{Ca}/P_{Cs}$ from 1.4 to 3.7. The effect was attributable to the removal of an electrostatic influence of the Arg-436 residue. Despite its relatively high permeability to $Ca^{2+},$ the single channel conductance of the $5-HT_{3A}(QDA)$ receptor was depressed in a concentration-dependent and voltage-independent manner by extracellular $Ca^{2+}.$ A conserved aspartate, located toward the extracellular end of the conduction pathway and known to influence ionic selectivity, contributed to the inhibitory effect of $Ca^{2+}$ on macroscopic currents mediated by $5-HT_{3A}$ receptors. We introduced a D293A mutation into the $5-HT_{3A}(QDA)$ receptor (yielding the $5-HT_{3A}(QDA$ D293A) construct) to determine whether the aspartate is required for the suppression of single channel conductance by $Ca^{2+}.$ The D293A mutation decreased the $P_{Ca}/P_{Cs}$ ratio to 0.25 and reduced inwardly directed single channel conductance from 41 to 30 pS but did not prevent suppression of single channel conductance by $Ca^{2+}.$ The D293A mutation also reduced $P_{Ca}/P_{Cs}$ when engineered into the wild-type $5-HT_{3A}$ receptor. The data helped to identify key residues in the cytoplasmic domain (Arg-436) and extracellular vestibule (Asp-293) that markedly influence $P_{Ca}/P_{Cs}$ and additionally directly demonstrated a depression of single channel conductance by $Ca^{2+}.$ |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| Journal | Journal of Biological Chemistry |
| Issue Number | 28 |
| Volume Number | 283 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology (United States) |
| Publisher Date | 2008-07-11 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Calcium Metabolism Cell Membrane Permeability Physiology Neurons Receptors, Serotonin, 5-HT3 Amino Acid Substitution Cell Line Ion Channel Gating Mutation Protein Structure, Tertiary Protein Subunits Genetics Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Biochemistry Molecular Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
National Digital Library of India (NDLI) is a virtual repository of learning resources which is not just a repository with search/browse facilities but provides a host of services for the learner community. It is sponsored and mentored by Ministry of Education, Government of India, through its National Mission on Education through Information and Communication Technology (NMEICT). Filtered and federated searching is employed to facilitate focused searching so that learners can find the right resource with least effort and in minimum time. NDLI provides user group-specific services such as Examination Preparatory for School and College students and job aspirants. Services for Researchers and general learners are also provided. NDLI is designed to hold content of any language and provides interface support for 10 most widely used Indian languages. It is built to provide support for all academic levels including researchers and life-long learners, all disciplines, all popular forms of access devices and differently-abled learners. It is designed to enable people to learn and prepare from best practices from all over the world and to facilitate researchers to perform inter-linked exploration from multiple sources. It is developed, operated and maintained from Indian Institute of Technology Kharagpur.
Learn more about this project from here.
NDLI is a conglomeration of freely available or institutionally contributed or donated or publisher managed contents. Almost all these contents are hosted and accessed from respective sources. The responsibility for authenticity, relevance, completeness, accuracy, reliability and suitability of these contents rests with the respective organization and NDLI has no responsibility or liability for these. Every effort is made to keep the NDLI portal up and running smoothly unless there are some unavoidable technical issues.
Ministry of Education, through its National Mission on Education through Information and Communication Technology (NMEICT), has sponsored and funded the National Digital Library of India (NDLI) project.
| Sl. | Authority | Responsibilities | Communication Details |
|---|---|---|---|
| 1 | Ministry of Education (GoI), Department of Higher Education |
Sanctioning Authority | https://www.education.gov.in/ict-initiatives |
| 2 | Indian Institute of Technology Kharagpur | Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project | https://www.iitkgp.ac.in |
| 3 | National Digital Library of India Office, Indian Institute of Technology Kharagpur | The administrative and infrastructural headquarters of the project | Dr. B. Sutradhar bsutra@ndl.gov.in |
| 4 | Project PI / Joint PI | Principal Investigator and Joint Principal Investigators of the project |
Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon |
| 5 | Website/Portal (Helpdesk) | Queries regarding NDLI and its services | support@ndl.gov.in |
| 6 | Contents and Copyright Issues | Queries related to content curation and copyright issues | content@ndl.gov.in |
| 7 | National Digital Library of India Club (NDLI Club) | Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach | clubsupport@ndl.gov.in |
| 8 | Digital Preservation Centre (DPC) | Assistance with digitizing and archiving copyright-free printed books | dpc@ndl.gov.in |
| 9 | IDR Setup or Support | Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops | idr@ndl.gov.in |
|
Loading...
|