Transfer of High Sensitivity for Benzothiazepines from L-type to Class A (BI) Calcium Channels
| Autor: | Martina J. Sinnegger, Jörg Striessnig, Jörg Mitterdorfer, Manfred Grabner, Frank Döring, Degtiar' Ve, Stanislav Berjukow, Zhengyi Wang, Steffen Hering, Stefan Aczél, Hartmut Glossmann |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
Gallopamil
Calcium Channels L-Type Stereochemistry Xenopus Molecular Sequence Data N-type calcium channel Biochemistry Diltiazem medicine Animals Amino Acid Sequence Molecular Biology Peptide sequence chemistry.chemical_classification Ion Transport Voltage-dependent calcium channel Chemistry Calcium channel Cell Biology Calcium Channel Blockers Amino acid Transmembrane domain Barium Calcium Channels Sequence Alignment medicine.drug |
| Zdroj: | Journal of Biological Chemistry. 271:24471-24475 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.271.40.24471 |
| Popis: | To investigate the molecular basis of the calcium channel block by diltiazem, we transferred amino acids of the highly sensitive and stereoselective L-type (alpha1S or alpha1C) to a weakly sensitive, nonstereoselective class A (alpha1A) calcium channel. Transfer of three amino acids of transmembrane segment IVS6 of L-type alpha1 into the alpha1A subunit (I1804Y, S1808A, and M1811I) was sufficient to support a use-dependent block by diltiazem and by the phenylalkylamine (-)-gallopamil after expression in Xenopus oocytes. An additional mutation F1805M increased the sensitivity for (-)-gallopamil but not for diltiazem. Our data suggest that the receptor domains for diltiazem and gallopamil have common but not identical molecular determinants in transmembrane segment IVS6. These mutations also identified single amino acid residues in segment IVS6 that are important for class A channel inactivation. |
| Databáze: | OpenAIRE |
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