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| Content Provider | PubMed Central |
|---|---|
| Author | Fuller-bicer, Geraldine A. Varadi, Gyula Koch, Sheryl E. Ishii, Masakazu Bodi, Ilona Kadeer, Nijiat Muth, James N. Mikala, Gabor Petrashevskaya, Natalia N. Jordan, Michael A. Zhang, Sui-po Qin, Ning Flores, Christopher M. Isaacsohn, Idit Varadi, Maria Mori, Yasuo Jones, W. Keith Schwartz, Arnold |
| Abstract | Cardiac L-type voltage-dependent Ca2+ channels are heteromultimeric polypeptide complexes of α1-, α2/δ-, and β-subunits. The α2/δ-1-subunit possesses a stereoselective, high-affinity binding site for gabapentin, widely used to treat epilepsy and postherpetic neuralgic pain as well as sleep disorders. Mutations in α2/δ-subunits of voltage-dependent Ca2+ channels have been associated with different diseases, including epilepsy. Multiple heterologous coexpression systems have been used to study the effects of the deletion of the α2/δ-1-subunit, but attempts at a conventional knockout animal model have been ineffective. We report the development of a viable conventional knockout mouse using a construct targeting exon 2 of α2/δ-1. While the deletion of the subunit is not lethal, these animals lack high-affinity gabapentin binding sites and demonstrate a significantly decreased basal myocardial contractility and relaxation and a decreased L-type Ca2+ current peak current amplitude. This is a novel model for studying the function of the α2/δ-1-subunit and will be of importance in the development of new pharmacological therapies. |
| Related Links | http://dx.doi.org/10.1152/ajpheart.00122.2009 |
| Starting Page | 117 |
| File Format | |
| ISSN | 03636135 |
| e-ISSN | 15221539 |
| Journal | American Journal of Physiology - Heart and Circulatory Physiology |
| Issue Number | 1 |
| Volume Number | 297 |
| Language | English |
| Publisher | American Physiological Society |
| Publisher Date | 2009-07-01 |
| Access Restriction | Open |
| Rights Holder | American Physiological Society |
| Subject Keyword | Physiology (medical) Physiology Cardiology and Cardiovascular Medicine Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Physiology Physiology (medical) Cardiology and Cardiovascular Medicine |
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