کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2532748 | 1559022 | 2011 | 8 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: A residue W756 in the P-loop segment of the sodium channel is critical for primaquine binding A residue W756 in the P-loop segment of the sodium channel is critical for primaquine binding](/preview/png/2532748.png)
Our study on the wild-type and mutants of the voltage-dependent sodium channel in the rat skeletal muscle Nav 1.4 was to examine the possible binding site of primaquine PQ by using an experimental approach. We used a standard voltage-clamp in oocytes. Previously, we had demonstrated that PQ blocks the voltage-dependent sodium current in rat myocytes and that this blocking is concentration-dependent and voltage-independent. The direct-site mutagenesis in the P-loop segment W402C, W756C, W1239C, W1531A at the outer tryptophan-rich lip, and D400C, E758C, K1237C, A1529C of the DEKA locus helped us to identify residues playing a key role in aminoquinoline binding. In full agreement with our computed results, where a 1000-fold reduction of inhibition was measured, the tryptophan 756 is crucial for the reversible modulating effects of PQ. The W756C decreased the blocking effect of PQ in voltage-clamp assays. This new binding site may be important to the development of new drugs that modulate sodium inward currents.
Journal: European Journal of Pharmacology - Volume 663, Issues 1–3, 1 August 2011, Pages 1–8